rs4389469

Positions:

• chr3-8882156-C-T

Variant summary

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

The NM_020165.4(RAD18):​c.1386-697G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,008 control chromosomes in the GnomAD database, including 14,164 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 0.42 (14164 hom., cov: 31)
• Consequence: RAD18 NM_020165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD18	NM_020165.4	c.1386-697G>A		intron_variant		ENST00000264926.7
RAD18	XM_017006873.2	c.1128-697G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD18	ENST00000264926.7	c.1386-697G>A		intron_variant		1	NM_020165.4	P1
RAD18	ENST00000427329.5	c.294+8233G>A		intron_variant		3
RAD18	ENST00000415439.5	c.*376-697G>A		intron_variant, NMD_transcript_variant		5
RAD18	ENST00000473069.1	n.517-697G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64396 AN: 151890 Hom.: 14150 Cov.: 31

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.424 AC: 64459 AN: 152008 Hom.: 14164 Cov.: 31 AF XY: 0.416 AC XY: 30894 AN XY: 74310

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.398

Alfa AF: 0.389 Hom.: 15473

Bravo AF: 0.432

Asia WGS AF: 0.358 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.38

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: rs4389469; hg19: chr3-8923840;