rs195420

chr6-37354031-C-Gchr6-37354031-C-T

Variant summary

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

The NM_003958.4(RNF8):c.-134C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 789,000 control chromosomes in the GnomAD database, including 14,979 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 0.24 (7803 hom., cov: 32)
  • Exomes 𝑓: 0.12 (7176 hom.)
• Consequence: RNF8 NM_003958.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540

Genes affected

RNF8 (HGNC:10071): (ring finger protein 8) The protein encoded by this gene contains a RING finger motif and an FHA domain. This protein has been shown to interact with several class II ubiquitin-conjugating enzymes (E2), including UBE2E1/UBCH6, UBE2E2, and UBE2E3, and may act as an ubiquitin ligase (E3) in the ubiquitination of certain nuclear proteins. This protein is also known to play a role in the DNA damage response and depletion of this protein causes cell growth inhibition and cell cycle arrest. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF8	NM_003958.4	c.-134C>G		5_prime_UTR_variant	1/8	ENST00000373479.9
RNF8	NM_183078.3	c.-134C>G		5_prime_UTR_variant	1/7
RNF8	NR_046399.2	n.49C>G		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF8	ENST00000373479.9	c.-134C>G		5_prime_UTR_variant	1/8	1	NM_003958.4	P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36689 AN: 152110 Hom.: 7796 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0822

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.119 AC: 75502 AN: 636772 Hom.: 7176 Cov.: 9 AF XY: 0.116 AC XY: 38264 AN XY: 330584

Gnomad4 AFR exome AF: 0.587

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.0796

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.0831

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.241 AC: 36726 AN: 152228 Hom.: 7803 Cov.: 32 AF XY: 0.240 AC XY: 17893 AN XY: 74442

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.0822

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.0849

Gnomad4 OTH AF: 0.211

Alfa AF: 0.0737 Hom.: 144

Bravo AF: 0.262

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	5.8
Dann	Benign	0.73

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: rs195420; hg19: chr6-37321807; COSMIC: COSV57721445; COSMIC: COSV57721445;