rs10841831

Positions:

• chr12-21475386-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002907.4(RECQL):​c.1216+82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 848,098 control chromosomes in the GnomAD database, including 99,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18150 hom., cov: 32)
  • Exomes 𝑓: 0.48 (81064 hom.)
• Consequence: RECQL NM_002907.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.23

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-21475386-C-T is Benign according to our data. Variant chr12-21475386-C-T is described in ClinVar as [Benign]. Clinvar id is 679688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL	NM_002907.4	c.1216+82G>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.1216+82G>A		intron_variant		2	NM_002907.4	ENSP00000416739	P1
RECQL	ENST00000421138.6	c.1216+82G>A		intron_variant		1		ENSP00000395449	P1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74034 AN: 151194 Hom.: 18122 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.491

GnomAD4 exome AF: 0.481 AC: 335120 AN: 696784 Hom.: 81064 AF XY: 0.478 AC XY: 174872 AN XY: 365898

Gnomad4 AFR exome AF: 0.502

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.560

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.498

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.487

GnomAD4 genome AF: 0.490 AC: 74106 AN: 151314 Hom.: 18150 Cov.: 32 AF XY: 0.489 AC XY: 36162 AN XY: 73894

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.497

Alfa AF: 0.484 Hom.: 2234

Bravo AF: 0.492

Asia WGS AF: 0.542 AC: 1884 AN: 3470

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	clinical testing	GeneDx	Jun 20, 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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.5
DANN	Benign	0.27

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: rs10841831; hg19: chr12-21628320;