rs3752648

Variant names:

• chr12-21475857-T-C
• rs3752648
• NM_002907.4:c.950-33A>G

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.950-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,544,720 control chromosomes in the GnomAD database, including 177,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18451 hom., cov: 33)
  • Exomes 𝑓: 0.48 (158575 hom.)
• Consequence: RECQL NM_002907.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.982
• Publications: 12 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=-0.78).
• BP6: Variant 12-21475857-T-C is Benign according to our data. Variant chr12-21475857-T-C is described in ClinVar as [Benign]. Clinvar id is 679686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL	NM_002907.4	c.950-33A>G		intron_variant	Intron 8 of 14	ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7	c.950-33A>G		intron_variant	Intron 8 of 14	2	NM_002907.4	ENSP00000416739.2
RECQL	ENST00000421138.6	c.950-33A>G		intron_variant	Intron 9 of 15	1		ENSP00000395449.2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74602 AN: 151742 Hom.: 18424 Cov.: 33

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.491

GnomAD2 exomes AF: 0.480 AC: 115804 AN: 241328 AF XY: 0.477

Gnomad AFR exome AF: 0.500

Gnomad AMR exome AF: 0.460

Gnomad ASJ exome AF: 0.429

Gnomad EAS exome AF: 0.566

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.479

Gnomad OTH exome AF: 0.489

GnomAD4 exome AF: 0.476 AC: 662925 AN: 1392860 Hom.: 158575 Cov.: 23 AF XY: 0.475 AC XY: 330385 AN XY: 696156

African (AFR) AF: 0.505 AC: 16212 AN: 32102

American (AMR) AF: 0.467 AC: 20684 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 10956 AN: 25648

East Asian (EAS) AF: 0.564 AC: 22152 AN: 39280

South Asian (SAS) AF: 0.437 AC: 37025 AN: 84658

European-Finnish (FIN) AF: 0.500 AC: 24544 AN: 49056

Middle Eastern (MID) AF: 0.525 AC: 2963 AN: 5646

European-Non Finnish (NFE) AF: 0.474 AC: 500083 AN: 1053992

Other (OTH) AF: 0.487 AC: 28306 AN: 58142

GnomAD4 genome AF: 0.492 AC: 74672 AN: 151860 Hom.: 18451 Cov.: 33 AF XY: 0.491 AC XY: 36474 AN XY: 74212

African (AFR) AF: 0.508 AC: 21068 AN: 41458

American (AMR) AF: 0.493 AC: 7517 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1447 AN: 3470

East Asian (EAS) AF: 0.544 AC: 2803 AN: 5156

South Asian (SAS) AF: 0.437 AC: 2108 AN: 4820

European-Finnish (FIN) AF: 0.498 AC: 5261 AN: 10564

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.483 AC: 32779 AN: 67820

Other (OTH) AF: 0.497 AC: 1049 AN: 2112

Alfa AF: 0.481 Hom.: 22292

Bravo AF: 0.493

Asia WGS AF: 0.546 AC: 1900 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.5
DANN	Benign	0.85
PhyloP100		0.98
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: rs3752648; hg19: chr12-21628791; COSMIC: COSV69658863; COSMIC: COSV69658863;