dbSNP rs10841834: RECQL:c.17-17C>T (chr12-21491733-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_002907.4(RECQL):c.17-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,589,552 control chromosomes in the GnomAD database, including 167,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12151 hom., cov: 31)

Exomes 𝑓: 0.46 ( 155473 hom. )

Consequence

RECQL
NM_002907.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

RECQL (HGNC:9948): (RecQ like helicase) The protein encoded by this gene is a member of the RecQ DNA helicase family. DNA helicases are enzymes involved in various types of DNA repair, including mismatch repair, nucleotide excision repair and direct repair. The encoded protein is involved in the processing of Holliday junctions, the suppression of sister chromatid exchanges, telomere maintenance, and is required for genotoxic stress resistance. Defects in this gene have been associated with several types of cancer. [provided by RefSeq, Jan 2017]

RECQL 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=-0.93).

BP6

Variant 12-21491733-G-A is Benign according to our data. Variant chr12-21491733-G-A is described in ClinVar as [Benign]. Clinvar id is 679680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL	NM_002907.4 link	c.17-17C>T		intron_variant	Intron 2 of 14	ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7 link	c.17-17C>T		intron_variant	Intron 2 of 14	2	NM_002907.4	ENSP00000416739.2		P46063

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57487

AN:

151814

Hom.:

12152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.407

Gnomad ASJ

AF:

0.468

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.361

GnomAD3 exomes

AF:

0.449

AC:

101327

AN:

225818

Hom.:

23223

AF XY:

0.454

AC XY:

55277

AN XY:

121716

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.484

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.448

Gnomad SAS exome

AF:

0.495

Gnomad FIN exome

AF:

0.487

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.441

GnomAD4 exome

AF:

0.462

AC:

664131

AN:

1437620

Hom.:

155473

Cov.:

AF XY:

0.463

AC XY:

330952

AN XY:

714328

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.468

Gnomad4 ASJ exome

AF:

0.462

Gnomad4 EAS exome

AF:

0.449

Gnomad4 SAS exome

AF:

0.493

Gnomad4 FIN exome

AF:

0.488

Gnomad4 NFE exome

AF:

0.470

Gnomad4 OTH exome

AF:

0.431

GnomAD4 genome

AF:

0.378

AC:

57501

AN:

151932

Hom.:

12151

Cov.:

AF XY:

0.382

AC XY:

28347

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.173

Gnomad4 AMR

AF:

0.407

Gnomad4 ASJ

AF:

0.468

Gnomad4 EAS

AF:

0.463

Gnomad4 SAS

AF:

0.496

Gnomad4 FIN

AF:

0.491

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.422

Hom.:

3597

Bravo

AF:

0.362

Asia WGS

AF:

0.407

AC:

1412

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.8

DANN

Benign

0.42

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