rs615967

chr3-8963394-C-T

Variant summary

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

The NM_020165.4(RAD18):c.-9G>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 0.76 in 1,587,240 control chromosomes in the GnomAD database, including 467,256 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 0.66 (35796 hom., cov: 29)
  • Exomes 𝑓: 0.77 (431460 hom.)
• Consequence: RAD18 NM_020165.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD18	NM_020165.4	c.-9G>A		5_prime_UTR_variant	1/13	ENST00000264926.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD18	ENST00000264926.7	c.-9G>A		5_prime_UTR_variant	1/13	1	NM_020165.4	P1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100390 AN: 151722 Hom.: 35793 Cov.: 29

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.700

GnomAD3 exomes AF: 0.740 AC: 165862 AN: 224202 Hom.: 63256 AF XY: 0.757 AC XY: 92864 AN XY: 122630

Gnomad AFR exome AF: 0.400

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.801

Gnomad EAS exome AF: 0.405

Gnomad SAS exome AF: 0.863

Gnomad FIN exome AF: 0.803

Gnomad NFE exome AF: 0.794

Gnomad OTH exome AF: 0.776

GnomAD4 exome AF: 0.770 AC: 1105243 AN: 1435400 Hom.: 431460 Cov.: 42 AF XY: 0.775 AC XY: 553127 AN XY: 714050

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.683

Gnomad4 ASJ exome AF: 0.796

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.858

Gnomad4 FIN exome AF: 0.799

Gnomad4 NFE exome AF: 0.789

Gnomad4 OTH exome AF: 0.741

GnomAD4 genome AF: 0.661 AC: 100420 AN: 151840 Hom.: 35796 Cov.: 29 AF XY: 0.666 AC XY: 49387 AN XY: 74198

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.703

Alfa AF: 0.763 Hom.: 85793

Bravo AF: 0.637

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.1
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs615967; hg19: chr3-9005078; COSMIC: COSV53750241;