rs195434

chr6-37392781-T-C

Variant summary

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

The NM_003958.4(RNF8):c.*2023T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 397,926 control chromosomes in the GnomAD database, including 10,313 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 0.23 (8018 hom., cov: 32)
  • Exomes 𝑓: 0.094 (2295 hom.)
• Consequence: RNF8 NM_003958.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF8	NM_003958.4	c.*2023T>C		3_prime_UTR_variant	8/8	ENST00000373479.9
RNF8	NM_183078.3	c.*1929T>C		3_prime_UTR_variant	7/7
RNF8	NR_046399.2	n.3769T>C		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF8	ENST00000373479.9	c.*2023T>C		3_prime_UTR_variant	8/8	1	NM_003958.4	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34290 AN: 152082 Hom.: 7989 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0495

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.0944 AC: 23188 AN: 245726 Hom.: 2295 Cov.: 0 AF XY: 0.0922 AC XY: 11477 AN XY: 124526

Gnomad4 AFR exome AF: 0.590

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.0966

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0472

Gnomad4 NFE exome AF: 0.0610

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.226 AC: 34367 AN: 152200 Hom.: 8018 Cov.: 32 AF XY: 0.221 AC XY: 16477 AN XY: 74438

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0495

Gnomad4 NFE AF: 0.0614

Gnomad4 OTH AF: 0.199

Alfa AF: 0.0896 Hom.: 1840

Bravo AF: 0.253

Asia WGS AF: 0.170 AC: 592 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.29
Dann	Benign	0.56

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: rs195434; hg19: chr6-37360557;