3-8841356-T-C

Position:

• chr3-8841356-T-C

Variant summary

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

The ENST00000427329.5(RAD18):​c.293+49033A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,056 control chromosomes in the GnomAD database, including 31,431 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 0.63 (31431 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAD18 ENST00000427329.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208

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]

CAV3 (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 (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107984112	XR_001740594.2	n.7188A>G		non_coding_transcript_exon_variant	3/3
LOC107984112	XR_001740593.2	n.8535+16A>G		intron_variant
LOC107984112	XR_007095814.1	n.8368-1059A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD18	ENST00000427329.5	c.293+49033A>G		intron_variant		3		ENSP00000412054.1
CAV3	ENST00000472766.1	n.228T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94924 AN: 151938 Hom.: 31371 Cov.: 33

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.574

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.625 AC: 95045 AN: 152056 Hom.: 31431 Cov.: 33 AF XY: 0.628 AC XY: 46667 AN XY: 74332

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.580

Alfa AF: 0.496 Hom.: 13412

Bravo AF: 0.632

Asia WGS AF: 0.672 AC: 2334 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	1.0
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2270474; hg19: chr3-8883040;