17-75630842-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004259.7(RECQL5):c.1586-6_1586-5insA variant causes a splice region, splice polypyrimidine tract, 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 (★).

• Frequency:
  • Genomes: 𝑓 0.60 (16451 hom., cov: 21)
  • Exomes 𝑓: 0.59 (180276 hom.)
• Consequence: RECQL5 NM_004259.7 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.258

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]

ACMG classification

Verdict is Benign. Variant got -10 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 id is 3059523.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL5	NM_004259.7	c.1586-6_1586-5insA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000317905.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL5	ENST00000317905.10	c.1586-6_1586-5insA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004259.7	P1
RECQL5	ENST00000423245.6	c.1505-6_1505-5insA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
RECQL5	ENST00000443199.6	n.1122-6_1122-5insA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
RECQL5	ENST00000580707.1	c.53-6_53-5insA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		3

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

GnomAD3 exomes AF: 0.387 AC: 22223 AN: 57474 Hom.: 3187 AF XY: 0.390 AC XY: 11280 AN XY: 28946

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 SAS exome AF: 0.383

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

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.536

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.621

Gnomad4 NFE exome AF: 0.595

Gnomad4 OTH exome AF: 0.582

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

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.597

Bravo AF: 0.0405

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

RECQL5-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 2019

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 v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs56158987; hg19: chr17-73626922; COSMIC: COSV58645226; COSMIC: COSV58645226;