rs369032

Variant names:

• chr3-8897519-G-A
• rs369032
• NM_020165.4:c.1322+1375C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020165.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD18	NM_020165.4	MANE Select	c.1322+1375C>T		intron	N/A	NP_064550.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD18	ENST00000264926.7	TSL:1 MANE Select	c.1322+1375C>T		intron	N/A	ENSP00000264926.2	Q9NS91
	RAD18	ENST00000956589.1		c.1178+1375C>T		intron	N/A	ENSP00000626648.1
	RAD18	ENST00000858877.1		c.599+1375C>T		intron	N/A	ENSP00000528936.1

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

African (AFR) AF: 0.121 AC: 5006 AN: 41472

American (AMR) AF: 0.559 AC: 8529 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2111 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1370 AN: 5156

South Asian (SAS) AF: 0.580 AC: 2788 AN: 4806

European-Finnish (FIN) AF: 0.605 AC: 6377 AN: 10540

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42049 AN: 67956

Other (OTH) AF: 0.512 AC: 1079 AN: 2108

Alfa AF: 0.550 Hom.: 47662

Bravo AF: 0.441

Asia WGS AF: 0.371 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.28
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs369032; hg19: chr3-8939203;