17-75630842-G-GT

Variant names:

• chr17-75630842-G-GT
• rs56158987
• NM_004259.7:c.1586-6_1586-5insA

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_004259.7(RECQL5):​c.1586-6_1586-5insA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,254,226 control chromosomes in the GnomAD database, including 196,727 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.60 (16451 hom., cov: 21)
  • Exomes 𝑓: 0.59 (180276 hom.)
• Consequence: RECQL5 NM_004259.7 splice_region, intron
• Clinical Significance: Benign no assertion criteria provided B:1
• 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 -9 ACMG points.

• BP6: Variant 17-75630842-G-GT is Benign according to our data. Variant chr17-75630842-G-GT is described in ClinVar as Benign. ClinVar VariationId is 3059523.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 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_1586-5insA		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_1586-5insA		splice_region intron	N/A	ENSP00000317636.5
	RECQL5	ENST00000423245.6	TSL:1	c.1505-6_1505-5insA		splice_region intron	N/A	ENSP00000394820.2
	RECQL5	ENST00000443199.6	TSL:1	n.1122-6_1122-5insA		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.598 AC: 64768 AN: 108364 Hom.: 16444 Cov.: 21

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.616

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.594

GnomAD2 exomes AF: 0.387 AC: 22223 AN: 57474 AF XY: 0.390

Gnomad AFR exome AF: 0.424

Gnomad AMR exome AF: 0.332

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.391

Gnomad FIN exome AF: 0.381

Gnomad NFE exome AF: 0.408

Gnomad OTH exome AF: 0.398

GnomAD4 exome AF: 0.591 AC: 676972 AN: 1145826 Hom.: 180276 Cov.: 25 AF XY: 0.591 AC XY: 331816 AN XY: 561020

African (AFR) AF: 0.400 AC: 8698 AN: 21772

American (AMR) AF: 0.603 AC: 13948 AN: 23134

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 8894 AN: 16596

East Asian (EAS) AF: 0.624 AC: 16109 AN: 25810

South Asian (SAS) AF: 0.592 AC: 34475 AN: 58228

European-Finnish (FIN) AF: 0.621 AC: 23352 AN: 37598

Middle Eastern (MID) AF: 0.515 AC: 2354 AN: 4568

European-Non Finnish (NFE) AF: 0.595 AC: 541897 AN: 911294

Other (OTH) AF: 0.582 AC: 27245 AN: 46826

GnomAD4 genome AF: 0.598 AC: 64791 AN: 108400 Hom.: 16451 Cov.: 21 AF XY: 0.603 AC XY: 31431 AN XY: 52154

African (AFR) AF: 0.536 AC: 11418 AN: 21314

American (AMR) AF: 0.585 AC: 6643 AN: 11346

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1461 AN: 2602

East Asian (EAS) AF: 0.586 AC: 2310 AN: 3940

South Asian (SAS) AF: 0.633 AC: 2245 AN: 3546

European-Finnish (FIN) AF: 0.654 AC: 4787 AN: 7320

Middle Eastern (MID) AF: 0.615 AC: 128 AN: 208

European-Non Finnish (NFE) AF: 0.617 AC: 34399 AN: 55780

Other (OTH) AF: 0.597 AC: 936 AN: 1568

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0405

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

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		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs56158987; hg19: chr17-73626922; COSMIC: COSV58645226; COSMIC: COSV58645226;