17-75630842-G-GTGT

Variant names:

• chr17-75630842-G-GTGT
• rs56158987
• NM_004259.7:c.1586-6_1586-5insACA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004259.7(RECQL5):​c.1586-6_1586-5insACA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 1,139,402 control chromosomes in the GnomAD database, including 1,959 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.059 (269 hom., cov: 21)
  • Exomes 𝑓: 0.063 (1959 hom.)
  • Failed GnomAD Quality Control
• Consequence: RECQL5 NM_004259.7 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.258
• Publications: 7 publications found

Genes affected

RECQL5 (HGNC:9950): (RecQ like helicase 5) The protein encoded by this gene is a helicase that is important for genome stability. The encoded protein also prevents aberrant homologous recombination by displacing RAD51 from ssDNA. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

RECQL5 Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• coronary artery disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-75630842-G-GTGT is Benign according to our data. Variant chr17-75630842-G-GTGT is described in ClinVar as Benign. ClinVar VariationId is 403370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004259.7. 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
	RECQL5	NM_004259.7	MANE Select	c.1586-6_1586-5insACA		splice_region intron	N/A	NP_004250.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL5	ENST00000317905.10	TSL:1 MANE Select	c.1586-6_1586-5insACA		splice_region intron	N/A	ENSP00000317636.5
	RECQL5	ENST00000423245.6	TSL:1	c.1505-6_1505-5insACA		splice_region intron	N/A	ENSP00000394820.2
	RECQL5	ENST00000443199.6	TSL:1	n.1122-6_1122-5insACA		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 6424 AN: 108212 Hom.: 269 Cov.: 21

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0391

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.00480

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0622

Gnomad MID AF: 0.0690

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.0531

GnomAD2 exomes AF: 0.124 AC: 7134 AN: 57474 AF XY: 0.122

Gnomad AFR exome AF: 0.0323

Gnomad AMR exome AF: 0.0790

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.0570

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.0631 AC: 71928 AN: 1139402 Hom.: 1959 Cov.: 25 AF XY: 0.0628 AC XY: 35040 AN XY: 557830

African (AFR) AF: 0.0135 AC: 294 AN: 21742

American (AMR) AF: 0.0320 AC: 740 AN: 23118

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 654 AN: 16556

East Asian (EAS) AF: 0.00380 AC: 98 AN: 25784

South Asian (SAS) AF: 0.0370 AC: 2148 AN: 58000

European-Finnish (FIN) AF: 0.0668 AC: 2498 AN: 37388

Middle Eastern (MID) AF: 0.0336 AC: 153 AN: 4552

European-Non Finnish (NFE) AF: 0.0694 AC: 62810 AN: 905644

Other (OTH) AF: 0.0543 AC: 2533 AN: 46618

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0593 AC: 6423 AN: 108248 Hom.: 269 Cov.: 21 AF XY: 0.0560 AC XY: 2916 AN XY: 52056

African (AFR) AF: 0.0202 AC: 431 AN: 21324

American (AMR) AF: 0.0390 AC: 442 AN: 11338

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 113 AN: 2598

East Asian (EAS) AF: 0.00456 AC: 18 AN: 3944

South Asian (SAS) AF: 0.0338 AC: 120 AN: 3548

European-Finnish (FIN) AF: 0.0622 AC: 454 AN: 7294

Middle Eastern (MID) AF: 0.0769 AC: 16 AN: 208

European-Non Finnish (NFE) AF: 0.0835 AC: 4645 AN: 55650

Other (OTH) AF: 0.0530 AC: 83 AN: 1566

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

RECQL5-related disorder Benign:1

Nov 04, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.26
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs56158987; hg19: chr17-73626922;