rs1061627

Positions:

• chr12-21501473-G-A
• chr12-21501473-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002907.4(RECQL):​c.-349C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 161,314 control chromosomes in the GnomAD database, including 41,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (38125 hom., cov: 27)
  • Exomes 𝑓: 0.79 (3214 hom.)
• Consequence: RECQL NM_002907.4 5_prime_UTR
• Scores: Splicing: ADA: 0.00007014
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.25

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 12-21501473-G-A is Benign according to our data. Variant chr12-21501473-G-A is described in ClinVar as [Benign]. Clinvar id is 679678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL	NM_002907.4	c.-349C>T		5_prime_UTR_variant	1/15	ENST00000444129.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL	ENST00000444129.7	c.-349C>T		5_prime_UTR_variant	1/15	2	NM_002907.4	P1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 102673 AN: 151160 Hom.: 38107 Cov.: 27

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.787 AC: 7902 AN: 10036 Hom.: 3214 Cov.: 0 AF XY: 0.794 AC XY: 4320 AN XY: 5440

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.796

Gnomad4 ASJ exome AF: 0.682

Gnomad4 EAS exome AF: 0.976

Gnomad4 SAS exome AF: 0.901

Gnomad4 FIN exome AF: 0.863

Gnomad4 NFE exome AF: 0.783

Gnomad4 OTH exome AF: 0.685

GnomAD4 genome AF: 0.679 AC: 102732 AN: 151278 Hom.: 38125 Cov.: 27 AF XY: 0.690 AC XY: 50949 AN XY: 73886

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.671

Alfa AF: 0.763 Hom.: 59419

Bravo AF: 0.656

Asia WGS AF: 0.867 AC: 3011 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.65
CADD	Benign	6.4
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000070
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.080		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: rs1061627; hg19: chr12-21654407;