dbSNP rs4244611: RECQL4:c.1621-15C>T (chr8-144514540-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_004260.4(RECQL4):c.1621-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,607,346 control chromosomes in the GnomAD database, including 175,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 13353 hom., cov: 34)

Exomes 𝑓: 0.47 ( 162403 hom. )

Consequence

RECQL4
NM_004260.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.100

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 (BayesDel_noAF=-0.81).

BP6

Variant 8-144514540-G-A is Benign according to our data. Variant chr8-144514540-G-A is described in ClinVar as [Benign]. Clinvar id is 94886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514540-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.1621-15C>T		intron_variant	Intron 9 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.1621-15C>T		intron_variant	Intron 9 of 20	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58849

AN:

152050

Hom.:

13348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.579

Gnomad FIN

AF:

0.502

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.473

Gnomad OTH

AF:

0.422

GnomAD3 exomes

AF:

0.477

AC:

114486

AN:

240224

Hom.:

28304

AF XY:

0.482

AC XY:

63204

AN XY:

131158

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.560

Gnomad ASJ exome

AF:

0.446

Gnomad EAS exome

AF:

0.469

Gnomad SAS exome

AF:

0.568

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.472

Gnomad OTH exome

AF:

0.467

GnomAD4 exome

AF:

0.468

AC:

680427

AN:

1455178

Hom.:

162403

Cov.:

AF XY:

0.472

AC XY:

341259

AN XY:

723420

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.549

Gnomad4 ASJ exome

AF:

0.435

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.564

Gnomad4 FIN exome

AF:

0.497

Gnomad4 NFE exome

AF:

0.470

Gnomad4 OTH exome

AF:

0.452

GnomAD4 genome

AF:

0.387

AC:

58860

AN:

152168

Hom.:

13353

Cov.:

AF XY:

0.395

AC XY:

29362

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.509

Gnomad4 ASJ

AF:

0.419

Gnomad4 EAS

AF:

0.470

Gnomad4 SAS

AF:

0.580

Gnomad4 FIN

AF:

0.502

Gnomad4 NFE

AF:

0.473

Gnomad4 OTH

AF:

0.421

Alfa

AF:

0.402

Hom.:

3201

Bravo

AF:

0.374

Asia WGS

AF:

0.533

AC:

1852

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

May 08, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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

- -

Rapadilino syndrome

Benign:2

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.55

DANN

Benign

0.74

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