rs195434

Variant names:

• chr6-37392781-T-C
• rs195434
• NM_003958.4:c.*2023T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003958.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF8	NM_003958.4	MANE Select	c.*2023T>C		3_prime_UTR	Exon 8 of 8	NP_003949.1	O76064-1
	RNF8	NM_183078.3		c.*1929T>C		3_prime_UTR	Exon 7 of 7	NP_898901.1	O76064-3
	RNF8	NR_046399.2		n.3769T>C		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF8	ENST00000373479.9	TSL:1 MANE Select	c.*2023T>C		3_prime_UTR	Exon 8 of 8	ENSP00000362578.4	O76064-1

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

African (AFR) AF: 0.590 AC: 4236 AN: 7178

American (AMR) AF: 0.171 AC: 1272 AN: 7432

Ashkenazi Jewish (ASJ) AF: 0.0966 AC: 892 AN: 9236

East Asian (EAS) AF: 0.154 AC: 3513 AN: 22846

South Asian (SAS) AF: 0.131 AC: 346 AN: 2644

European-Finnish (FIN) AF: 0.0472 AC: 982 AN: 20800

Middle Eastern (MID) AF: 0.121 AC: 156 AN: 1294

European-Non Finnish (NFE) AF: 0.0610 AC: 9640 AN: 157938

Other (OTH) AF: 0.131 AC: 2151 AN: 16358

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

African (AFR) AF: 0.599 AC: 24854 AN: 41486

American (AMR) AF: 0.173 AC: 2653 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3470

East Asian (EAS) AF: 0.119 AC: 619 AN: 5190

South Asian (SAS) AF: 0.141 AC: 679 AN: 4820

European-Finnish (FIN) AF: 0.0495 AC: 524 AN: 10596

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0614 AC: 4178 AN: 68022

Other (OTH) AF: 0.199 AC: 422 AN: 2116

Alfa AF: 0.106 Hom.: 4177

Bravo AF: 0.253

Asia WGS AF: 0.170 AC: 592 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.29
DANN	Benign	0.56
PhyloP100		-1.6
Mutation Taster		=100/0	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: rs195434; hg19: chr6-37360557;