rs593205

Positions:

• chr3-8899910-G-C
• chr3-8899910-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.1169-863C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 152,226 control chromosomes in the GnomAD database, including 311 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 0.055 (311 hom., cov: 32)
• Consequence: RAD18 NM_020165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676

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]

RAD18 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD18	NM_020165.4	c.1169-863C>G		intron_variant		ENST00000264926.7	NP_064550.3
RAD18	XM_017006873.2	c.911-863C>G		intron_variant			XP_016862362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD18	ENST00000264926.7	c.1169-863C>G		intron_variant		1	NM_020165.4	ENSP00000264926.2

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 8310 AN: 152108 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0856

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0473

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

GnomAD4 genome AF: 0.0546 AC: 8304 AN: 152226 Hom.: 311 Cov.: 32 AF XY: 0.0529 AC XY: 3937 AN XY: 74424

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0330

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0503

Gnomad4 FIN AF: 0.0856

Gnomad4 NFE AF: 0.0856

Gnomad4 OTH AF: 0.0458

Alfa AF: 0.0390 Hom.: 34

Bravo AF: 0.0486

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.77

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: rs593205; hg19: chr3-8941594;