rs1860947

Positions:

• chr12-21501710-C-A
• chr12-21501710-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The 12-21501710-C-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 600,312 control chromosomes in the GnomAD database, including 227,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (54906 hom., cov: 33)
  • Exomes 𝑓: 0.88 (172722 hom.)
• Consequence: RECQL ENST00000396093.7 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.40

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 12-21501710-C-A is Benign according to our data. Variant chr12-21501710-C-A is described in ClinVar as [Benign]. Clinvar id is 679677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000314748.10			upstream_gene_variant		5		ENSP00000318727
RECQL	ENST00000396093.7			upstream_gene_variant		5		ENSP00000379400
RECQL	ENST00000536240.5			upstream_gene_variant		4		ENSP00000439069

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128956 AN: 152104 Hom.: 54874 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.848

GnomAD4 exome AF: 0.877 AC: 392828 AN: 448090 Hom.: 172722 Cov.: 2 AF XY: 0.878 AC XY: 207303 AN XY: 236176

Gnomad4 AFR exome AF: 0.771

Gnomad4 AMR exome AF: 0.906

Gnomad4 ASJ exome AF: 0.804

Gnomad4 EAS exome AF: 0.981

Gnomad4 SAS exome AF: 0.919

Gnomad4 FIN exome AF: 0.888

Gnomad4 NFE exome AF: 0.865

Gnomad4 OTH exome AF: 0.858

GnomAD4 genome AF: 0.848 AC: 129037 AN: 152222 Hom.: 54906 Cov.: 33 AF XY: 0.852 AC XY: 63426 AN XY: 74428

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.883

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.921

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.850

Alfa AF: 0.855 Hom.: 50681

Bravo AF: 0.844

Asia WGS AF: 0.938 AC: 3260 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.71
CADD	Benign	0.019
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1860947; hg19: chr12-21654644;