rs1061626

Positions:

• chr12-21501535-T-G

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.-411A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 231,458 control chromosomes in the GnomAD database, including 5,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5008 hom., cov: 30)
  • Exomes 𝑓: 0.13 (878 hom.)
• Consequence: RECQL NM_002907.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.51

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=-0.68).
• BP6: Variant 12-21501535-T-G is Benign according to our data. Variant chr12-21501535-T-G is described in ClinVar as [Benign]. Clinvar id is 679709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL	NM_002907.4	c.-411A>C		5_prime_UTR_variant	1/15	ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7	c.-411A>C		5_prime_UTR_variant	1/15	2	NM_002907.4	ENSP00000416739	P1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33025 AN: 148852 Hom.: 5008 Cov.: 30

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.125 AC: 10326 AN: 82494 Hom.: 878 Cov.: 0 AF XY: 0.122 AC XY: 5379 AN XY: 44256

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.00416

Gnomad4 SAS exome AF: 0.0692

Gnomad4 FIN exome AF: 0.0815

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.222 AC: 33047 AN: 148964 Hom.: 5008 Cov.: 30 AF XY: 0.215 AC XY: 15615 AN XY: 72784

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.0785

Gnomad4 FIN AF: 0.0920

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.229

Alfa AF: 0.175 Hom.: 2690

Bravo AF: 0.235

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 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.6
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs1061626; hg19: chr12-21654469;