rs10841834

chr12-21491733-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002907.4(RECQL):c.17-17C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
RECQL	NM_002907.4	c.17-17C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000444129.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL	ENST00000444129.7	c.17-17C>T		splice_polypyrimidine_tract_variant, intron_variant		2	NM_002907.4	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57487 AN: 151814 Hom.: 12152 Cov.: 31

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

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.: 29 AF XY: 0.463 AC XY: 330952 AN XY: 714328

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.: 31 AF XY: 0.382 AC XY: 28347 AN XY: 74256

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

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

Other links and lift over

dbSNP: rs10841834; hg19: chr12-21644667; COSMIC: COSV59084253;