rs369032

chr3-8897519-G-A

Variant summary

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

The NM_020165.4(RAD18):c.1322+1375C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,978 control chromosomes in the GnomAD database, including 19,947 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 0.46 (19947 hom., cov: 31)
• Consequence: RAD18 NM_020165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD18	NM_020165.4	c.1322+1375C>T		intron_variant		ENST00000264926.7
RAD18	XM_017006873.2	c.1064+1375C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD18	ENST00000264926.7	c.1322+1375C>T		intron_variant		1	NM_020165.4	P1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70099 AN: 151860 Hom.: 19953 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.461 AC: 70079 AN: 151978 Hom.: 19947 Cov.: 31 AF XY: 0.464 AC XY: 34488 AN XY: 74278

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.512

Alfa AF: 0.596 Hom.: 36842

Bravo AF: 0.441

Asia WGS AF: 0.371 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.0
Dann	Benign	0.28

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: rs369032; hg19: chr3-8939203;