rs12423412

Variant names:

• chr12-21499707-G-A
• rs12423412
• NM_002907.4:c.-45-92C>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.-45-92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 623,600 control chromosomes in the GnomAD database, including 17,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3283 hom., cov: 33)
  • Exomes 𝑓: 0.24 (13964 hom.)
• Consequence: RECQL NM_002907.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.400
• Publications: 4 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=-0.91).
• BP6: Variant 12-21499707-G-A is Benign according to our data. Variant chr12-21499707-G-A is described in ClinVar as Benign. ClinVar VariationId is 679679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL	NM_002907.4	c.-45-92C>T		intron_variant	Intron 1 of 14	ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7	c.-45-92C>T		intron_variant	Intron 1 of 14	2	NM_002907.4	ENSP00000416739.2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28632 AN: 151984 Hom.: 3279 Cov.: 33

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.236 AC: 111172 AN: 471498 Hom.: 13964 AF XY: 0.237 AC XY: 59189 AN XY: 249480

African (AFR) AF: 0.0480 AC: 545 AN: 11364

American (AMR) AF: 0.265 AC: 4058 AN: 15340

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 2253 AN: 13054

East Asian (EAS) AF: 0.318 AC: 9238 AN: 29026

South Asian (SAS) AF: 0.274 AC: 10216 AN: 37294

European-Finnish (FIN) AF: 0.220 AC: 9577 AN: 43508

Middle Eastern (MID) AF: 0.214 AC: 661 AN: 3086

European-Non Finnish (NFE) AF: 0.235 AC: 69068 AN: 293390

Other (OTH) AF: 0.218 AC: 5556 AN: 25436

GnomAD4 genome AF: 0.188 AC: 28640 AN: 152102 Hom.: 3283 Cov.: 33 AF XY: 0.191 AC XY: 14228 AN XY: 74356

African (AFR) AF: 0.0478 AC: 1986 AN: 41522

American (AMR) AF: 0.244 AC: 3723 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3466

East Asian (EAS) AF: 0.294 AC: 1519 AN: 5170

South Asian (SAS) AF: 0.281 AC: 1355 AN: 4822

European-Finnish (FIN) AF: 0.218 AC: 2303 AN: 10544

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.243 AC: 16504 AN: 67982

Other (OTH) AF: 0.204 AC: 430 AN: 2108

Alfa AF: 0.210 Hom.: 605

Bravo AF: 0.184

Asia WGS AF: 0.306 AC: 1064 AN: 3472

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	-0.91
CADD	Benign	0.48
DANN	Benign	0.64
PhyloP100		-0.40
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: rs12423412; hg19: chr12-21652641;