rs820200

Positions:

• chr17-75635950-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004259.7(RECQL5):​c.1230-4282G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 736,904 control chromosomes in the GnomAD database, including 43,093 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8158 hom., cov: 33)
  • Exomes 𝑓: 0.34 (34935 hom.)
• Consequence: RECQL5 NM_004259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

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]

SMIM5 (HGNC:40030): (small integral membrane protein 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

RECQL5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL5	NM_004259.7	c.1230-4282G>T		intron_variant		ENST00000317905.10	NP_004250.4
SMIM5	NM_001162995.3	c.-37+1748C>A		intron_variant		ENST00000375215.3	NP_001156467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL5	ENST00000317905.10	c.1230-4282G>T		intron_variant		1	NM_004259.7	ENSP00000317636.5
SMIM5	ENST00000375215.3	c.-37+1748C>A		intron_variant		1	NM_001162995.3	ENSP00000364363.3
RECQL5	ENST00000423245.6	c.1149-4282G>T		intron_variant		1		ENSP00000394820.2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48685 AN: 152066 Hom.: 8159 Cov.: 33

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.344 AC: 201394 AN: 584720 Hom.: 34935 AF XY: 0.345 AC XY: 94396 AN XY: 273506

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.394

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.401

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.320 AC: 48702 AN: 152184 Hom.: 8158 Cov.: 33 AF XY: 0.323 AC XY: 24054 AN XY: 74376

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.323

Alfa AF: 0.330 Hom.: 1386

Bravo AF: 0.323

Asia WGS AF: 0.396 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.3
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs820200; hg19: chr17-73632030; COSMIC: COSV58638698; COSMIC: COSV58638698;