chr3-8939458-G-A

Position:

• chr3-8939458-G-A

Variant summary

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

The NM_020165.4(RAD18):​c.704+96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 978,598 control chromosomes in the GnomAD database, including 294 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 0.026 (175 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (119 hom.)
• Consequence: RAD18 NM_020165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

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 = 0.0863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD18	NM_020165.4	c.704+96C>T		intron_variant		ENST00000264926.7	NP_064550.3
RAD18	XM_017006873.2	c.446+96C>T		intron_variant			XP_016862362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD18	ENST00000264926.7	c.704+96C>T		intron_variant		1	NM_020165.4	ENSP00000264926	P1
RAD18	ENST00000415439.5	c.704+96C>T		intron_variant, NMD_transcript_variant		5		ENSP00000402049

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3942 AN: 151970 Hom.: 174 Cov.: 32

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.00288 AC: 2378 AN: 826510 Hom.: 119 AF XY: 0.00242 AC XY: 1030 AN XY: 425898

Gnomad4 AFR exome AF: 0.0934

Gnomad4 AMR exome AF: 0.00683

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000323

Gnomad4 FIN exome AF: 0.0000207

Gnomad4 NFE exome AF: 0.000208

Gnomad4 OTH exome AF: 0.00696

GnomAD4 genome AF: 0.0260 AC: 3948 AN: 152088 Hom.: 175 Cov.: 32 AF XY: 0.0247 AC XY: 1838 AN XY: 74376

Gnomad4 AFR AF: 0.0886

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0243 Hom.: 20

Bravo AF: 0.0305

Asia WGS AF: 0.00433 AC: 16 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	3.1
DANN	Benign	0.35

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: rs11922749; hg19: chr3-8981142;