rs4987216

Variant names:

• chr12-21490464-C-T
• rs4987216
• NM_002907.4:c.215-86G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002907.4(RECQL):​c.215-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 814,608 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (17 hom., cov: 32)
  • Exomes 𝑓: 0.017 (134 hom.)
• Consequence: RECQL NM_002907.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.169
• Publications: 1 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 12-21490464-C-T is Benign according to our data. Variant chr12-21490464-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1210631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0129 (1972/152300) while in subpopulation NFE AF = 0.0217 (1475/68020). AF 95% confidence interval is 0.0208. There are 17 homozygotes in GnomAd4. There are 885 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL	NM_002907.4	c.215-86G>A		intron_variant	Intron 3 of 14	ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7	c.215-86G>A		intron_variant	Intron 3 of 14	2	NM_002907.4	ENSP00000416739.2

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1974 AN: 152182 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00348

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0173

GnomAD4 exome AF: 0.0171 AC: 11302 AN: 662308 Hom.: 134 AF XY: 0.0166 AC XY: 5774 AN XY: 347720

African (AFR) AF: 0.00356 AC: 60 AN: 16876

American (AMR) AF: 0.00762 AC: 195 AN: 25600

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 206 AN: 16326

East Asian (EAS) AF: 0.00 AC: 0 AN: 34106

South Asian (SAS) AF: 0.000305 AC: 16 AN: 52426

European-Finnish (FIN) AF: 0.0200 AC: 682 AN: 34074

Middle Eastern (MID) AF: 0.00690 AC: 19 AN: 2752

European-Non Finnish (NFE) AF: 0.0215 AC: 9636 AN: 447278

Other (OTH) AF: 0.0148 AC: 488 AN: 32870

GnomAD4 genome AF: 0.0129 AC: 1972 AN: 152300 Hom.: 17 Cov.: 32 AF XY: 0.0119 AC XY: 885 AN XY: 74498

African (AFR) AF: 0.00347 AC: 144 AN: 41558

American (AMR) AF: 0.00843 AC: 129 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.0138 AC: 146 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0217 AC: 1475 AN: 68020

Other (OTH) AF: 0.0171 AC: 36 AN: 2108

Alfa AF: 0.0171 Hom.: 5

Bravo AF: 0.0124

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.16
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism

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: rs4987216; hg19: chr12-21643398;