rs1061626

Variant names:

• chr12-21501535-T-G
• rs1061626
• NM_002907.4:c.-411A>C

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.-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
• Publications: 19 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=-0.68).
• BP6: Variant 12-21501535-T-G is Benign according to our data. Variant chr12-21501535-T-G is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002907.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	NM_002907.4	MANE Select	c.-411A>C		5_prime_UTR	Exon 1 of 15	NP_002898.2
	RECQL	NM_032941.3		c.-214A>C		5_prime_UTR	Exon 1 of 16	NP_116559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	ENST00000444129.7	TSL:2 MANE Select	c.-411A>C		5_prime_UTR	Exon 1 of 15	ENSP00000416739.2
	RECQL	ENST00000421138.6	TSL:1	c.-214A>C		5_prime_UTR	Exon 1 of 16	ENSP00000395449.2
	RECQL	ENST00000396093.7	TSL:5	c.-164A>C		5_prime_UTR	Exon 1 of 7	ENSP00000379400.3

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

African (AFR) AF: 0.435 AC: 918 AN: 2110

American (AMR) AF: 0.122 AC: 362 AN: 2962

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 416 AN: 2432

East Asian (EAS) AF: 0.00416 AC: 14 AN: 3362

South Asian (SAS) AF: 0.0692 AC: 942 AN: 13622

European-Finnish (FIN) AF: 0.0815 AC: 388 AN: 4758

Middle Eastern (MID) AF: 0.255 AC: 76 AN: 298

European-Non Finnish (NFE) AF: 0.133 AC: 6441 AN: 48362

Other (OTH) AF: 0.168 AC: 769 AN: 4588

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

African (AFR) AF: 0.449 AC: 17462 AN: 38882

American (AMR) AF: 0.174 AC: 2626 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 699 AN: 3468

East Asian (EAS) AF: 0.0106 AC: 54 AN: 5086

South Asian (SAS) AF: 0.0785 AC: 376 AN: 4788

European-Finnish (FIN) AF: 0.0920 AC: 963 AN: 10470

Middle Eastern (MID) AF: 0.333 AC: 96 AN: 288

European-Non Finnish (NFE) AF: 0.148 AC: 10023 AN: 67912

Other (OTH) AF: 0.229 AC: 474 AN: 2072

Alfa AF: 0.182 Hom.: 3924

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 20, 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.6
DANN	Benign	0.73
PhyloP100		-1.5
PromoterAI		0.0030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1061626; hg19: chr12-21654469;