Variant rs4251692 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_004260.4(RECQL4):c.3393+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,610,494 control chromosomes in the GnomAD database, including 685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 51 hom., cov: 34)

Exomes 𝑓: 0.027 ( 634 hom. )

Consequence

RECQL4
NM_004260.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.998

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 -16 ACMG points.

BP6

Variant 8-144511902-T-C is Benign according to our data. Variant chr8-144511902-T-C is described in ClinVar as [Benign]. Clinvar id is 259260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144511902-T-C is described in Lovd as [Likely_benign]. Variant chr8-144511902-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0203 (3089/152362) while in subpopulation NFE AF= 0.0279 (1895/68026). AF 95% confidence interval is 0.0268. There are 51 homozygotes in gnomad4. There are 1483 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4 linkuse as main transcript	c.3393+9A>G		intron_variant		ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6 linkuse as main transcript	c.3393+9A>G		intron_variant		1	NM_004260.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

3089

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00593

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.0770

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0380

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0279

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0231

AC:

5664

AN:

245642

Hom.:

AF XY:

0.0232

AC XY:

3115

AN XY:

134086

show subpopulations

Gnomad AFR exome

AF:

0.00444

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0761

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00566

Gnomad FIN exome

AF:

0.0377

Gnomad NFE exome

AF:

0.0296

Gnomad OTH exome

AF:

0.0297

GnomAD4 exome

AF:

0.0270

AC:

39370

AN:

1458132

Hom.:

634

Cov.:

AF XY:

0.0267

AC XY:

19373

AN XY:

725394

show subpopulations

Gnomad4 AFR exome

AF:

0.00475

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.0757

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00477

Gnomad4 FIN exome

AF:

0.0371

Gnomad4 NFE exome

AF:

0.0292

Gnomad4 OTH exome

AF:

0.0295

GnomAD4 genome

AF:

0.0203

AC:

3089

AN:

152362

Hom.:

Cov.:

AF XY:

0.0199

AC XY:

1483

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00592

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.0770

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00517

Gnomad4 FIN

AF:

0.0380

Gnomad4 NFE

AF:

0.0279

Gnomad4 OTH

AF:

0.0198

Alfa

AF:

0.0247

Hom.:

Bravo

AF:

0.0193

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0320

EpiControl

AF:

0.0289

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

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

- -

Baller-Gerold syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.19

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.35

Position offset: 0

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