rs604092

Positions:

• chr3-8963697-C-T

Variant summary

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

The ENST00000413832.1(RAD18):​c.-230G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 259,388 control chromosomes in the GnomAD database, including 80,071 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 0.77 (45522 hom., cov: 34)
  • Exomes 𝑓: 0.79 (34549 hom.)
• Consequence: RAD18 ENST00000413832.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

Genes affected

RAD18 (HGNC:18278): (RAD18 E3 ubiquitin protein ligase) The protein encoded by this gene is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through its interaction with Rad6, which is an ubiquitin-conjugating enzyme required for post-replication repair of damaged DNA. Similar to its yeast counterpart, this protein is able to interact with the human homolog of yeast Rad6 protein through a conserved ring-finger motif. Mutation of this motif results in defective replication of UV-damaged DNA and hypersensitivity to multiple mutagens. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.8963697C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD18	ENST00000413832.1	c.-230G>A		5_prime_UTR_variant	1/6	5		ENSP00000412261.1

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116767 AN: 152138 Hom.: 45498 Cov.: 34

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.794 AC: 85030 AN: 107132 Hom.: 34549 Cov.: 2 AF XY: 0.801 AC XY: 44428 AN XY: 55486

Gnomad4 AFR exome AF: 0.686

Gnomad4 AMR exome AF: 0.774

Gnomad4 ASJ exome AF: 0.853

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.920

Gnomad4 FIN exome AF: 0.822

Gnomad4 NFE exome AF: 0.830

Gnomad4 OTH exome AF: 0.786

GnomAD4 genome AF: 0.767 AC: 116841 AN: 152256 Hom.: 45522 Cov.: 34 AF XY: 0.767 AC XY: 57067 AN XY: 74444

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.883

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.785

Alfa AF: 0.770 Hom.: 8961

Bravo AF: 0.754

Asia WGS AF: 0.642 AC: 2236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.7
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs604092; hg19: chr3-9005381;