6-37354031-C-G

Variant names:

• chr6-37354031-C-G
• rs195420
• NM_003958.4:c.-134C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003958.4(RNF8):​c.-134C>G variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNF8	NM_003958.4	c.-134C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	ENST00000373479.9	NP_003949.1
RNF8	NM_003958.4	c.-134C>G		5_prime_UTR_variant	Exon 1 of 8	ENST00000373479.9	NP_003949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF8	ENST00000373479.9	c.-134C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	1	NM_003958.4	ENSP00000362578.4
RNF8	ENST00000373479.9	c.-134C>G		5_prime_UTR_variant	Exon 1 of 8	1	NM_003958.4	ENSP00000362578.4

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

African (AFR) AF: 0.587 AC: 9370 AN: 15952

American (AMR) AF: 0.162 AC: 4723 AN: 29194

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 1393 AN: 17492

East Asian (EAS) AF: 0.289 AC: 8667 AN: 29988

South Asian (SAS) AF: 0.118 AC: 6949 AN: 58700

European-Finnish (FIN) AF: 0.138 AC: 5372 AN: 38968

Middle Eastern (MID) AF: 0.134 AC: 368 AN: 2750

European-Non Finnish (NFE) AF: 0.0831 AC: 34168 AN: 411390

Other (OTH) AF: 0.139 AC: 4492 AN: 32338

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

African (AFR) AF: 0.576 AC: 23924 AN: 41502

American (AMR) AF: 0.167 AC: 2555 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0822 AC: 285 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1318 AN: 5180

South Asian (SAS) AF: 0.137 AC: 660 AN: 4828

European-Finnish (FIN) AF: 0.151 AC: 1606 AN: 10612

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0849 AC: 5775 AN: 68024

Other (OTH) AF: 0.211 AC: 445 AN: 2112

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
PhyloP100		-0.54
PromoterAI		-0.20	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

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