chr3-8963394-C-T

Variant names:

• chr3-8963394-C-T
• rs615967
• NM_020165.4:c.-9G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020165.4(RAD18):​c.-9G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,587,240 control chromosomes in the GnomAD database, including 467,256 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 0.66 (35796 hom., cov: 29)
  • Exomes 𝑓: 0.77 (431460 hom.)
• Consequence: RAD18 NM_020165.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• Publications: 15 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.823 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD18	NM_020165.4	MANE Select	c.-9G>A		5_prime_UTR	Exon 1 of 13	NP_064550.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD18	ENST00000264926.7	TSL:1 MANE Select	c.-9G>A		5_prime_UTR	Exon 1 of 13	ENSP00000264926.2
	RAD18	ENST00000415439.5	TSL:5	n.-9G>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000402049.1
	RAD18	ENST00000469793.1	TSL:2	n.50G>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100390 AN: 151722 Hom.: 35793 Cov.: 29

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.700

GnomAD2 exomes AF: 0.740 AC: 165862 AN: 224202 AF XY: 0.757

Gnomad AFR exome AF: 0.400

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.801

Gnomad EAS exome AF: 0.405

Gnomad FIN exome AF: 0.803

Gnomad NFE exome AF: 0.794

Gnomad OTH exome AF: 0.776

GnomAD4 exome AF: 0.770 AC: 1105243 AN: 1435400 Hom.: 431460 Cov.: 42 AF XY: 0.775 AC XY: 553127 AN XY: 714050

African (AFR) AF: 0.383 AC: 12302 AN: 32126

American (AMR) AF: 0.683 AC: 29317 AN: 42910

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 20291 AN: 25494

East Asian (EAS) AF: 0.420 AC: 15568 AN: 37068

South Asian (SAS) AF: 0.858 AC: 71642 AN: 83476

European-Finnish (FIN) AF: 0.799 AC: 41767 AN: 52272

Middle Eastern (MID) AF: 0.831 AC: 4729 AN: 5692

European-Non Finnish (NFE) AF: 0.789 AC: 865947 AN: 1097402

Other (OTH) AF: 0.741 AC: 43680 AN: 58960

GnomAD4 genome AF: 0.661 AC: 100420 AN: 151840 Hom.: 35796 Cov.: 29 AF XY: 0.666 AC XY: 49387 AN XY: 74198

African (AFR) AF: 0.392 AC: 16215 AN: 41410

American (AMR) AF: 0.713 AC: 10887 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2764 AN: 3472

East Asian (EAS) AF: 0.382 AC: 1945 AN: 5098

South Asian (SAS) AF: 0.845 AC: 4046 AN: 4788

European-Finnish (FIN) AF: 0.790 AC: 8350 AN: 10572

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53731 AN: 67920

Other (OTH) AF: 0.703 AC: 1480 AN: 2104

Alfa AF: 0.743 Hom.: 121215

Bravo AF: 0.637

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.1
DANN	Benign	0.79
PhyloP100		-0.24
PromoterAI		-0.0090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs615967; hg19: chr3-9005078; COSMIC: COSV53750241;