rs341783

Variant names:

• chr3-8907067-A-G
• rs341783
• NM_020165.4:c.1028-4547T>C

Variant summary

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

The NM_020165.4(RAD18):​c.1028-4547T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,160 control chromosomes in the GnomAD database, including 53,322 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 0.84 (53322 hom., cov: 32)
• Consequence: RAD18 NM_020165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD18	NM_020165.4	c.1028-4547T>C		intron_variant	Intron 9 of 12	ENST00000264926.7	NP_064550.3
RAD18	XM_017006873.2	c.770-4547T>C		intron_variant	Intron 7 of 10		XP_016862362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD18	ENST00000264926.7	c.1028-4547T>C		intron_variant	Intron 9 of 12	1	NM_020165.4	ENSP00000264926.2
RAD18	ENST00000415439.5	n.*18-4547T>C		intron_variant	Intron 8 of 11	5		ENSP00000402049.1
RAD18	ENST00000473069.1	n.159-4547T>C		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.835 AC: 127021 AN: 152040 Hom.: 53280 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.835 AC: 127120 AN: 152160 Hom.: 53322 Cov.: 32 AF XY: 0.836 AC XY: 62192 AN XY: 74378

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.901

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.839

Alfa AF: 0.822 Hom.: 8133

Bravo AF: 0.830

Asia WGS AF: 0.738 AC: 2570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.61

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: rs341783; hg19: chr3-8948751;