rs4987216

Positions:

• chr12-21490464-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL	NM_002907.4	c.215-86G>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.215-86G>A		intron_variant		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

Gnomad4 AFR exome AF: 0.00356

Gnomad4 AMR exome AF: 0.00762

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000305

Gnomad4 FIN exome AF: 0.0200

Gnomad4 NFE exome AF: 0.0215

Gnomad4 OTH exome AF: 0.0148

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

Gnomad4 AFR AF: 0.00347

Gnomad4 AMR AF: 0.00843

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.0217

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0137 Hom.: 0

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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.16

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: rs4987216; hg19: chr12-21643398;