rs35159698

chr12-21474738-C-G

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.1355+103G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,116,032 control chromosomes in the GnomAD database, including 127,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16524 hom., cov: 34)
  • Exomes 𝑓: 0.48 (110593 hom.)
• Consequence: RECQL NM_002907.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0360

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=-0.86).
• BP6: Variant 12-21474738-C-G is Benign according to our data. Variant chr12-21474738-C-G is described in ClinVar as [Benign]. Clinvar id is 679690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL	NM_002907.4	c.1355+103G>C		intron_variant		ENST00000444129.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL	ENST00000444129.7	c.1355+103G>C		intron_variant		2	NM_002907.4	P1
RECQL	ENST00000421138.6	c.1355+103G>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70353 AN: 151834 Hom.: 16502 Cov.: 34

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.478 AC: 460608 AN: 964080 Hom.: 110593 AF XY: 0.475 AC XY: 233662 AN XY: 491534

Gnomad4 AFR exome AF: 0.405

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.546

Gnomad4 SAS exome AF: 0.420

Gnomad4 FIN exome AF: 0.502

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.463 AC: 70409 AN: 151952 Hom.: 16524 Cov.: 34 AF XY: 0.463 AC XY: 34435 AN XY: 74296

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.473

Alfa AF: 0.470 Hom.: 2117

Bravo AF: 0.462

Asia WGS AF: 0.518 AC: 1804 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 20, 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	-0.86
Cadd	Benign	4.0
Dann	Benign	0.40

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: rs35159698; hg19: chr12-21627672; COSMIC: COSV53710056; COSMIC: COSV53710056;