rs1168402

Positions:

• chr5-69411545-T-A
• chr5-69411545-T-C

Variant summary

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

The ENST00000354868.10(RAD17):​c.1751+995T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,006 control chromosomes in the GnomAD database, including 17,413 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 (17413 hom., cov: 31)
• Consequence: RAD17 ENST00000354868.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD17	NM_133338.3	c.1751+995T>A		intron_variant		ENST00000354868.10	NP_579916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD17	ENST00000354868.10	c.1751+995T>A		intron_variant		1	NM_133338.3	ENSP00000346938

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72419 AN: 151890 Hom.: 17416 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.477 AC: 72447 AN: 152006 Hom.: 17413 Cov.: 31 AF XY: 0.484 AC XY: 35977 AN XY: 74272

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.474

Alfa AF: 0.486 Hom.: 2410

Bravo AF: 0.466

Asia WGS AF: 0.509 AC: 1770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.66

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: rs1168402; hg19: chr5-68707372; COSMIC: COSV51456963; COSMIC: COSV51456963;