rs4251691

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004260.4(RECQL4):c.3014G>A(p.Arg1005Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,608,656 control chromosomes in the GnomAD database, including 170,115 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1005W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.38 ( 12828 hom., cov: 35)

Exomes 𝑓: 0.46 ( 157287 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12O:1

Conservation

PhyloP100: 0.622

Publications

47 publications found

Variant links:

Genes affected

RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

RECQL4 Gene-Disease associations (from GenCC):

Baller-Gerold syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
Rothmund-Thomson syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Rothmund-Thomson syndrome type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
osteosarcoma
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
rapadilino syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

RECQL4 links:

ENSG00000265393 (HGNC:):

ENSG00000265393 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.8596988E-4).

BP6

Variant 8-144512433-C-T is Benign according to our data. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512433-C-T is described in CliVar as Benign. Clinvar id is 94891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.3014G>A	p.Arg1005Gln	missense_variant	Exon 17 of 21	ENST00000617875.6	NP_004251.4	O94761

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6 link	c.3014G>A	p.Arg1005Gln	missense_variant	Exon 17 of 21	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57446

AN:

152076

Hom.:

12822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.581

Gnomad FIN

AF:

0.498

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.414

GnomAD2 exomes

AF:

0.467

AC:

113725

AN:

243454

AF XY:

0.473

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.557

Gnomad ASJ exome

AF:

0.408

Gnomad EAS exome

AF:

0.441

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.466

Gnomad OTH exome

AF:

0.456

GnomAD4 exome

AF:

0.460

AC:

669553

AN:

1456462

Hom.:

157287

Cov.:

AF XY:

0.464

AC XY:

335978

AN XY:

723870

show subpopulations

African (AFR)

AF:

0.110

AC:

3681

AN:

33432

American (AMR)

AF:

0.545

AC:

24238

AN:

44514

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

10466

AN:

26064

East Asian (EAS)

AF:

0.399

AC:

15800

AN:

39580

South Asian (SAS)

AF:

0.561

AC:

48313

AN:

86130

European-Finnish (FIN)

AF:

0.494

AC:

25367

AN:

51398

Middle Eastern (MID)

AF:

0.344

AC:

1980

AN:

5758

European-Non Finnish (NFE)

AF:

0.463

AC:

513225

AN:

1109448

Other (OTH)

AF:

0.440

AC:

26483

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

23142

46284

69426

92568

115710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15212

30424

45636

60848

76060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.378

AC:

57456

AN:

152194

Hom.:

12828

Cov.:

AF XY:

0.385

AC XY:

28681

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.126

AC:

5248

AN:

41534

American (AMR)

AF:

0.504

AC:

7709

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1328

AN:

3472

East Asian (EAS)

AF:

0.443

AC:

2287

AN:

5168

South Asian (SAS)

AF:

0.581

AC:

2808

AN:

4834

European-Finnish (FIN)

AF:

0.498

AC:

5279

AN:

10596

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.465

AC:

31600

AN:

67976

Other (OTH)

AF:

0.412

AC:

872

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1717

3434

5152

6869

8586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.408

Hom.:

6383

Bravo

AF:

0.364

TwinsUK

AF:

0.456

AC:

1689

ALSPAC

AF:

0.464

AC:

1789

ESP6500AA

AF:

0.128

AC:

543

ESP6500EA

AF:

0.448

AC:

3802

ExAC

AF:

0.452

AC:

54259

Asia WGS

AF:

0.505

AC:

1757

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4Other:1

May 08, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Rapadilino syndrome

Benign:2

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 24, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Rothmund-Thomson syndrome type 2

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Baller-Gerold syndrome

Benign:2

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.56

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.024

T;T;T

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.00039

T;T;T

MutationAssessor

Benign

0.81

.;L;.

PhyloP100

0.62

PrimateAI

Benign

0.22

Sift4G

Benign

0.29

T;T;T

Polyphen

0.035

.;B;.

Vest4

0.059

GERP RS

0.28

PromoterAI

0.017

Neutral

(source)

Varity_R

0.063

gMVP

0.60

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over