rs195420

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-37354031-C-A
• chr6-37354031-C-G
• chr6-37354031-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003958.4(RNF8):​c.-134C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000314 in 637,196 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: RNF8 NM_003958.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF8	NM_003958.4	c.-134C>A		5_prime_UTR_variant	Exon 1 of 8	ENST00000373479.9	NP_003949.1
RNF8	NR_046399.2	n.49C>A		non_coding_transcript_exon_variant	Exon 1 of 8
RNF8	NM_183078.3	c.-134C>A		5_prime_UTR_variant	Exon 1 of 7		NP_898901.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000314 AC: 2 AN: 637196 Hom.: 0 Cov.: 9 AF XY: 0.00000302 AC XY: 1 AN XY: 330796

African (AFR) AF: 0.00 AC: 0 AN: 15974

American (AMR) AF: 0.00 AC: 0 AN: 29208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17496

East Asian (EAS) AF: 0.00 AC: 0 AN: 30012

South Asian (SAS) AF: 0.0000341 AC: 2 AN: 58726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 411672

Other (OTH) AF: 0.00 AC: 0 AN: 32360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.5
DANN	Benign	0.76
PhyloP100		-0.54
PromoterAI		-0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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;