chr8-144512966-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004260.4(RECQL4):c.2636C>A(p.Pro879His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00995 in 1,571,768 control chromosomes in the GnomAD database, including 97 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. P879A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0089 ( 7 hom., cov: 34)

Exomes 𝑓: 0.010 ( 90 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 0.280

Publications

10 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=0.004400462).

BP6

Variant 8-144512966-G-T is Benign according to our data. Variant chr8-144512966-G-T is described in ClinVar as Benign. ClinVar VariationId is 94890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0089 (1355/152308) while in subpopulation AMR AF = 0.0157 (240/15308). AF 95% confidence interval is 0.0141. There are 7 homozygotes in GnomAd4. There are 633 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.2636C>A	p.Pro879His	missense_variant	Exon 15 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.2636C>A	p.Pro879His	missense_variant	Exon 15 of 21	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.00890

AC:

1355

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00511

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.00763

AC:

1399

AN:

183400

AF XY:

0.00768

show subpopulations

Gnomad AFR exome

AF:

0.00429

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.0131

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000742

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0101

AC:

14291

AN:

1419460

Hom.:

Cov.:

AF XY:

0.00994

AC XY:

6980

AN XY:

702330

show subpopulations

African (AFR)

AF:

0.00480

AC:

156

AN:

32484

American (AMR)

AF:

0.0115

AC:

441

AN:

38372

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

331

AN:

25454

East Asian (EAS)

AF:

0.00

AC:

AN:

37310

South Asian (SAS)

AF:

0.00311

AC:

253

AN:

81294

European-Finnish (FIN)

AF:

0.00118

AC:

AN:

49098

Middle Eastern (MID)

AF:

0.0284

AC:

162

AN:

5714

European-Non Finnish (NFE)

AF:

0.0112

AC:

12220

AN:

1090910

Other (OTH)

AF:

0.0114

AC:

670

AN:

58824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

938

1875

2813

3750

4688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.00890

AC:

1355

AN:

152308

Hom.:

Cov.:

AF XY:

0.00850

AC XY:

633

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00508

AC:

211

AN:

41570

American (AMR)

AF:

0.0157

AC:

240

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00228

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0113

AC:

767

AN:

68008

Other (OTH)

AF:

0.0137

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

157

236

314

393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00724

Hom.:

Bravo

AF:

0.00965

ESP6500AA

AF:

0.00403

AC:

ESP6500EA

AF:

0.00759

AC:

ExAC

AF:

0.00559

AC:

660

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RECQL4: BP4, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2Other:1

Dec 02, 2021

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Mar 04, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Rapadilino syndrome

Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Rothmund-Thomson syndrome type 2

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Baller-Gerold syndrome

Benign:1

Feb 02, 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

0.083

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Benign

0.50

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.027

T;T

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.31

T;T

MetaRNN

Benign

0.0044

T;T

MutationAssessor

Benign

1.5

.;L

PhyloP100

0.28

PrimateAI

Benign

0.32

Sift4G

Benign

0.13

T;T

Polyphen

0.39

.;B

Vest4

0.23

MVP

0.74

GERP RS

0.48

PromoterAI

-0.0062

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.034

gMVP

0.33

Mutation Taster

=97/3

polymorphism

(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