rs299086

chr5-69413682-G-Achr5-69413682-G-T

Variant summary

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

The NM_133338.3(RAD17):c.1752-349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,764 control chromosomes in the GnomAD database, including 17,555 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 0.48 (17555 hom., cov: 31)
• Consequence: RAD17 NM_133338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

Genes affected

RAD17 (HGNC:9807): (RAD17 checkpoint clamp loader component) The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad17, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This protein shares strong similarity with DNA replication factor C (RFC), and can form a complex with RFCs. This protein binds to chromatin prior to DNA damage and is phosphorylated by the checkpoint kinase ATR following damage. This protein recruits the RAD1-RAD9-HUS1 checkpoint protein complex onto chromatin after DNA damage, which may be required for its phosphorylation. The phosphorylation of this protein is required for the DNA-damage-induced cell cycle G2 arrest, and is thought to be a critical early event during checkpoint signaling in DNA-damaged cells. Multiple alternatively spliced transcript variants of this gene, which encode four distinct protein isoforms, have been reported. Two pseudogenes, located on chromosomes 7 and 13, have been identified. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD17	NM_133338.3	c.1752-349G>A		intron_variant		ENST00000354868.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD17	ENST00000354868.10	c.1752-349G>A		intron_variant		1	NM_133338.3

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72691 AN: 151644 Hom.: 17556 Cov.: 31

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.477

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.479 AC: 72724 AN: 151764 Hom.: 17555 Cov.: 31 AF XY: 0.487 AC XY: 36101 AN XY: 74136

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.481

Alfa AF: 0.373 Hom.: 1096

Bravo AF: 0.469

Asia WGS AF: 0.510 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.17
Dann	Benign	0.48

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: rs299086; hg19: chr5-68709509; COSMIC: COSV51456973; COSMIC: COSV51456973;