rs1860947

Variant names:

• chr12-21501710-C-A
• rs1860947
• NM_002907.4:c.-586G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-21501710-C-A
• chr12-21501710-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002907.4(RECQL):​c.-586G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 600,312 control chromosomes in the GnomAD database, including 227,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (54906 hom., cov: 33)
  • Exomes 𝑓: 0.88 (172722 hom.)
• Consequence: RECQL NM_002907.4 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.40
• Publications: 11 publications found

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]

GOLT1B (HGNC:20175): (golgi transport 1B) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. Located in endoplasmic reticulum. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 12-21501710-C-A is Benign according to our data. Variant chr12-21501710-C-A is described in ClinVar as Benign. ClinVar VariationId is 679677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL	NM_002907.4	c.-586G>T		upstream_gene_variant		ENST00000444129.7	NP_002898.2
GOLT1B	NM_016072.5	c.-214C>A		upstream_gene_variant		ENST00000229314.10	NP_057156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7	c.-586G>T		upstream_gene_variant		2	NM_002907.4	ENSP00000416739.2
GOLT1B	ENST00000229314.10	c.-214C>A		upstream_gene_variant		1	NM_016072.5	ENSP00000229314.4

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128956 AN: 152104 Hom.: 54874 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.848

GnomAD4 exome AF: 0.877 AC: 392828 AN: 448090 Hom.: 172722 Cov.: 2 AF XY: 0.878 AC XY: 207303 AN XY: 236176

African (AFR) AF: 0.771 AC: 9195 AN: 11924

American (AMR) AF: 0.906 AC: 16843 AN: 18594

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 10748 AN: 13362

East Asian (EAS) AF: 0.981 AC: 29019 AN: 29568

South Asian (SAS) AF: 0.919 AC: 41658 AN: 45344

European-Finnish (FIN) AF: 0.888 AC: 35357 AN: 39802

Middle Eastern (MID) AF: 0.806 AC: 1602 AN: 1988

European-Non Finnish (NFE) AF: 0.865 AC: 226416 AN: 261874

Other (OTH) AF: 0.858 AC: 21990 AN: 25634

GnomAD4 genome AF: 0.848 AC: 129037 AN: 152222 Hom.: 54906 Cov.: 33 AF XY: 0.852 AC XY: 63426 AN XY: 74428

African (AFR) AF: 0.773 AC: 32072 AN: 41500

American (AMR) AF: 0.883 AC: 13517 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2782 AN: 3472

East Asian (EAS) AF: 0.982 AC: 5083 AN: 5174

South Asian (SAS) AF: 0.921 AC: 4437 AN: 4820

European-Finnish (FIN) AF: 0.890 AC: 9445 AN: 10608

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58827 AN: 68016

Other (OTH) AF: 0.850 AC: 1799 AN: 2116

Alfa AF: 0.853 Hom.: 74419

Bravo AF: 0.844

Asia WGS AF: 0.938 AC: 3260 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.71
CADD	Benign	0.019
DANN	Benign	0.79
PhyloP100		-4.4
PromoterAI		0.042	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1860947; hg19: chr12-21654644;