rs1005989

chr3-8853172-T-Achr3-8853172-T-Cchr3-8853172-T-G

Variant summary

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

The XR_001740594.2(LOC107984112):n.6935-224A>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,882 control chromosomes in the GnomAD database, including 10,045 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 0.36 (10045 hom., cov: 31)
• Consequence: LOC107984112 XR_001740594.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782

Genes affected

LOC107984112 (HGNC:):

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC107984112	XR_001740594.2	n.6935-224A>T		intron_variant, non_coding_transcript_variant
LOC107984112	XR_001740593.2	n.8074A>T		non_coding_transcript_exon_variant	1/3
LOC107984112	XR_007095814.1	n.8074A>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD18	ENST00000427329.5	c.294+37217A>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54344 AN: 151764 Hom.: 10035 Cov.: 31

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.358 AC: 54380 AN: 151882 Hom.: 10045 Cov.: 31 AF XY: 0.359 AC XY: 26669 AN XY: 74242

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.339

Alfa AF: 0.234 Hom.: 573

Bravo AF: 0.347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.61
Dann	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1005989; hg19: chr3-8894856;