rs35159698

Variant names:

• chr12-21474738-C-G
• rs35159698
• NM_002907.4:c.1355+103G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-21474738-C-G
• chr12-21474738-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0360
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• RECON progeroid syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 679690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL	NM_002907.4	c.1355+103G>C		intron_variant	Intron 11 of 14	ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7	c.1355+103G>C		intron_variant	Intron 11 of 14	2	NM_002907.4	ENSP00000416739.2
RECQL	ENST00000421138.6	c.1355+103G>C		intron_variant	Intron 12 of 15	1		ENSP00000395449.2

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

African (AFR) AF: 0.405 AC: 9692 AN: 23904

American (AMR) AF: 0.464 AC: 16996 AN: 36628

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 8425 AN: 19720

East Asian (EAS) AF: 0.546 AC: 20060 AN: 36740

South Asian (SAS) AF: 0.420 AC: 27368 AN: 65158

European-Finnish (FIN) AF: 0.502 AC: 23008 AN: 45842

Middle Eastern (MID) AF: 0.509 AC: 1663 AN: 3268

European-Non Finnish (NFE) AF: 0.482 AC: 332589 AN: 689566

Other (OTH) AF: 0.481 AC: 20807 AN: 43254

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

African (AFR) AF: 0.413 AC: 17108 AN: 41472

American (AMR) AF: 0.481 AC: 7341 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3466

East Asian (EAS) AF: 0.528 AC: 2734 AN: 5178

South Asian (SAS) AF: 0.418 AC: 2015 AN: 4818

European-Finnish (FIN) AF: 0.499 AC: 5275 AN: 10568

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32816 AN: 67860

Other (OTH) AF: 0.473 AC: 1000 AN: 2114

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 20, 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.

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.40
PhyloP100		0.036
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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