rs4244610

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.3236+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,599,570 control chromosomes in the GnomAD database, including 177,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14483 hom., cov: 35)

Exomes 𝑓: 0.47 ( 163048 hom. )

Consequence

RECQL4
NM_004260.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.90

Publications

17 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:

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 (BayesDel_noAF=-0.8).

BP6

Variant 8-144512131-G-A is Benign according to our data. Variant chr8-144512131-G-A is described in ClinVar as Benign. ClinVar VariationId is 94893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.3236+13C>T		intron_variant	Intron 18 of 20	ENST00000617875.6	NP_004251.4	O94761

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6 link	c.3236+13C>T		intron_variant	Intron 18 of 20	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63981

AN:

152070

Hom.:

14478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.453

GnomAD2 exomes

AF:

0.490

AC:

112458

AN:

229620

AF XY:

0.493

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.571

Gnomad ASJ exome

AF:

0.455

Gnomad EAS exome

AF:

0.465

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.479

Gnomad OTH exome

AF:

0.475

GnomAD4 exome

AF:

0.472

AC:

682849

AN:

1447382

Hom.:

163048

Cov.:

AF XY:

0.476

AC XY:

341743

AN XY:

718472

show subpopulations

African (AFR)

AF:

0.242

AC:

8039

AN:

33262

American (AMR)

AF:

0.558

AC:

24136

AN:

43226

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

11503

AN:

25862

East Asian (EAS)

AF:

0.413

AC:

16196

AN:

39256

South Asian (SAS)

AF:

0.565

AC:

48191

AN:

85232

European-Finnish (FIN)

AF:

0.496

AC:

24929

AN:

50262

Middle Eastern (MID)

AF:

0.362

AC:

2084

AN:

5750

European-Non Finnish (NFE)

AF:

0.471

AC:

520263

AN:

1104784

Other (OTH)

AF:

0.460

AC:

27508

AN:

59748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

21319

42639

63958

85278

106597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15438

30876

46314

61752

77190

<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:

0.421

AC:

64001

AN:

152188

Hom.:

14483

Cov.:

AF XY:

0.427

AC XY:

31765

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.252

AC:

10463

AN:

41548

American (AMR)

AF:

0.523

AC:

7996

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1481

AN:

3466

East Asian (EAS)

AF:

0.466

AC:

2412

AN:

5176

South Asian (SAS)

AF:

0.587

AC:

2835

AN:

4826

European-Finnish (FIN)

AF:

0.499

AC:

5291

AN:

10594

Middle Eastern (MID)

AF:

0.425

AC:

124

AN:

292

European-Non Finnish (NFE)

AF:

0.474

AC:

32200

AN:

67960

Other (OTH)

AF:

0.451

AC:

954

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1863

3727

5590

7454

9317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.444

Hom.:

2851

Bravo

AF:

0.414

Asia WGS

AF:

0.534

AC:

1856

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

May 08, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Baller-Gerold syndrome

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Rapadilino syndrome

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Rothmund-Thomson syndrome type 2

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.094

(source)

DANN

Benign

0.90

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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