rs13088787

Positions:

• chr3-8961440-G-T

Variant summary

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

The NM_020165.4(RAD18):​c.51+1895C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,070 control chromosomes in the GnomAD database, including 6,166 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 0.23 (6166 hom., cov: 32)
• Consequence: RAD18 NM_020165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD18	NM_020165.4	c.51+1895C>A		intron_variant		ENST00000264926.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD18	ENST00000264926.7	c.51+1895C>A		intron_variant		1	NM_020165.4	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34641 AN: 151950 Hom.: 6142 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0215

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0769

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.228 AC: 34718 AN: 152070 Hom.: 6166 Cov.: 32 AF XY: 0.221 AC XY: 16450 AN XY: 74368

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.0769

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.192

Alfa AF: 0.175 Hom.: 1015

Bravo AF: 0.242

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.2
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13088787; hg19: chr3-9003124;