8-144517095-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004260.4(RECQL4):c.309G>A(p.Pro103Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,612,434 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P103P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0055 ( 5 hom., cov: 34)

Exomes 𝑓: 0.0056 ( 53 hom. )

Consequence

RECQL4
NM_004260.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.32

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 8-144517095-C-T is Benign according to our data. Variant chr8-144517095-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 239756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517095-C-T is described in Lovd as [Benign]. Variant chr8-144517095-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.32 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.309G>A	p.Pro103Pro	synonymous_variant	Exon 4 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.309G>A	p.Pro103Pro	synonymous_variant	Exon 4 of 21	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.00549

AC:

836

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00351

Gnomad FIN

AF:

0.0297

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00541

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00655

AC:

1616

AN:

246722

Hom.:

AF XY:

0.00654

AC XY:

881

AN XY:

134674

show subpopulations

Gnomad AFR exome

AF:

0.000722

Gnomad AMR exome

AF:

0.00186

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00546

Gnomad FIN exome

AF:

0.0293

Gnomad NFE exome

AF:

0.00504

Gnomad OTH exome

AF:

0.00867

GnomAD4 exome

AF:

0.00562

AC:

8212

AN:

1460048

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

3986

AN XY:

726300

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.0134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00516

Gnomad4 FIN exome

AF:

0.0283

Gnomad4 NFE exome

AF:

0.00486

Gnomad4 OTH exome

AF:

0.00671

GnomAD4 genome

AF:

0.00549

AC:

836

AN:

152386

Hom.:

Cov.:

AF XY:

0.00648

AC XY:

483

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.000793

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0297

Gnomad4 NFE

AF:

0.00541

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00623

Hom.:

Bravo

AF:

0.00354

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00463

EpiControl

AF:

0.00492

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RECQL4: BP4, BP7, BS2 -

Sep 01, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Feb 15, 2021

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Oct 02, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

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 03, 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

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.1

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over