rs2035221

chr3-8899187-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.1169-140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 567,726 control chromosomes in the GnomAD database, including 2,164 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 0.070 (489 hom., cov: 32)
  • Exomes 𝑓: 0.082 (1675 hom.)
• Consequence: RAD18 NM_020165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

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=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD18	NM_020165.4	c.1169-140G>A		intron_variant		ENST00000264926.7
RAD18	XM_017006873.2	c.911-140G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD18	ENST00000264926.7	c.1169-140G>A		intron_variant		1	NM_020165.4	P1

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10589 AN: 152132 Hom.: 486 Cov.: 32

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.0774

GnomAD4 exome AF: 0.0818 AC: 33966 AN: 415476 Hom.: 1675 AF XY: 0.0837 AC XY: 17802 AN XY: 212682

Gnomad4 AFR exome AF: 0.0230

Gnomad4 AMR exome AF: 0.0506

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.0196

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.0617

Gnomad4 NFE exome AF: 0.0881

Gnomad4 OTH exome AF: 0.0838

GnomAD4 genome AF: 0.0696 AC: 10596 AN: 152250 Hom.: 489 Cov.: 32 AF XY: 0.0687 AC XY: 5115 AN XY: 74448

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.0613

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.0233

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0533

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.0775

Alfa AF: 0.0822 Hom.: 63

Bravo AF: 0.0644

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	1.6
Dann	Benign	0.81

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: rs2035221; hg19: chr3-8940871;