rs2721190

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004260.4(RECQL4):c.274T>C(p.Ser92Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,612,104 control chromosomes in the GnomAD database, including 789,429 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 73726 hom., cov: 38)

Exomes 𝑓: 0.99 ( 715703 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.157

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.1035216E-7).

BP6

Variant 8-144517130-A-G is Benign according to our data. Variant chr8-144517130-A-G is described in ClinVar as [Benign]. Clinvar id is 135161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144517130-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.274T>C	p.Ser92Pro	missense_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.274T>C	p.Ser92Pro	missense_variant	Exon 4 of 21	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.983

AC:

149666

AN:

152260

Hom.:

73665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.983

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.949

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.804

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.986

GnomAD3 exomes

AF:

0.970

AC:

237760

AN:

245198

Hom.:

115679

AF XY:

0.975

AC XY:

130847

AN XY:

134138

show subpopulations

Gnomad AFR exome

AF:

0.982

Gnomad AMR exome

AF:

0.902

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

0.803

Gnomad SAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.997

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.981

GnomAD4 exome

AF:

0.989

AC:

1444084

AN:

1459726

Hom.:

715703

Cov.:

AF XY:

0.990

AC XY:

718854

AN XY:

726162

show subpopulations

Gnomad4 AFR exome

AF:

0.984

Gnomad4 AMR exome

AF:

0.908

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

0.758

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

0.996

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.989

GnomAD4 genome

AF:

0.983

AC:

149786

AN:

152378

Hom.:

73726

Cov.:

AF XY:

0.982

AC XY:

73148

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.983

Gnomad4 AMR

AF:

0.949

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

0.804

Gnomad4 SAS

AF:

0.997

Gnomad4 FIN

AF:

0.998

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.986

Alfa

AF:

0.994

Hom.:

68224

Bravo

AF:

0.978

TwinsUK

AF:

1.00

AC:

3707

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.986

AC:

3869

ESP6500EA

AF:

0.999

AC:

8276

ExAC

AF:

0.973

AC:

116620

Asia WGS

AF:

0.945

AC:

3285

AN:

3478

EpiCase

AF:

0.999

EpiControl

AF:

0.999

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not specified

Benign:1Other:1

Aug 02, 2012

Eurofins Ntd Llc (ga)

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

- -

Rapadilino syndrome

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.5

DANN

Benign

0.45

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.13

MetaRNN

Benign

8.1e-7

PrimateAI

Benign

0.34

Sift4G

Benign

0.39

Vest4

0.041

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.070

gMVP

0.14

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