rs11046076

Positions:

• chr12-21471375-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_002907.4(RECQL):​c.1667+53T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (11225 hom., cov: 25)
  • Exomes 𝑓: 0.61 (123009 hom.)
  • Failed GnomAD Quality Control
• Consequence: RECQL NM_002907.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00600

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-21471375-A-T is Benign according to our data. Variant chr12-21471375-A-T is described in ClinVar as [Benign]. Clinvar id is 679695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL	NM_002907.4	c.1667+53T>A		intron_variant		ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7	c.1667+53T>A		intron_variant		2	NM_002907.4	ENSP00000416739.2
RECQL	ENST00000421138.6	c.1667+53T>A		intron_variant		1		ENSP00000395449.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 54687 AN: 99574 Hom.: 11228 Cov.: 25 FAILED QC

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.512

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.528

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.612 AC: 560033 AN: 914676 Hom.: 123009 Cov.: 14 AF XY: 0.614 AC XY: 280746 AN XY: 457500

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.624

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.567

Gnomad4 SAS exome AF: 0.644

Gnomad4 FIN exome AF: 0.659

Gnomad4 NFE exome AF: 0.618

Gnomad4 OTH exome AF: 0.589

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.549 AC: 54687 AN: 99638 Hom.: 11225 Cov.: 25 AF XY: 0.554 AC XY: 27192 AN XY: 49068

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.527

Alfa AF: 0.368 Hom.: 1040

Bravo AF: 0.340

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 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	-0.88
CADD	Benign	0.15
DANN	Benign	0.42

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: rs11046076; hg19: chr12-21624309; COSMIC: COSV53710106; COSMIC: COSV53710106;