rs604092

Variant names:

• chr3-8963697-C-T
• rs604092
• ENST00000413832.1:c.-230G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAD18	NM_020165.4	c.-312G>A		upstream_gene_variant		ENST00000264926.7	NP_064550.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD18	ENST00000264926.7	c.-312G>A		upstream_gene_variant		1	NM_020165.4	ENSP00000264926.2

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

African (AFR) AF: 0.686 AC: 2463 AN: 3592

American (AMR) AF: 0.774 AC: 2762 AN: 3568

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 3633 AN: 4258

East Asian (EAS) AF: 0.421 AC: 3666 AN: 8714

South Asian (SAS) AF: 0.920 AC: 6357 AN: 6912

European-Finnish (FIN) AF: 0.822 AC: 5066 AN: 6162

Middle Eastern (MID) AF: 0.870 AC: 470 AN: 540

European-Non Finnish (NFE) AF: 0.830 AC: 55018 AN: 66264

Other (OTH) AF: 0.786 AC: 5595 AN: 7122

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

African (AFR) AF: 0.685 AC: 28476 AN: 41548

American (AMR) AF: 0.757 AC: 11583 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2983 AN: 3472

East Asian (EAS) AF: 0.384 AC: 1984 AN: 5172

South Asian (SAS) AF: 0.883 AC: 4267 AN: 4830

European-Finnish (FIN) AF: 0.814 AC: 8636 AN: 10614

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56171 AN: 67996

Other (OTH) AF: 0.785 AC: 1660 AN: 2114

Alfa AF: 0.767 Hom.: 9155

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
PhyloP100		-0.11
PromoterAI		-0.0078	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs604092; hg19: chr3-9005381;