rs34150698

Positions:

• chr6-37381290-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_003958.4(RNF8):​c.1377G>A​(p.Lys459Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 1,614,066 control chromosomes in the GnomAD database, including 4,063 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 0.056 (330 hom., cov: 32)
  • Exomes 𝑓: 0.067 (3733 hom.)
• Consequence: RNF8 NM_003958.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

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]

RNF8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=0.333 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF8	NM_003958.4	c.1377G>A	p.Lys459Lys	synonymous_variant	7/8	ENST00000373479.9	NP_003949.1
RNF8	NM_183078.3	c.1236+4257G>A		intron_variant			NP_898901.1
RNF8	NR_046399.2	n.1665G>A		non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF8	ENST00000373479.9	c.1377G>A	p.Lys459Lys	synonymous_variant	7/8	1	NM_003958.4	ENSP00000362578.4

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8509 AN: 152164 Hom.: 330 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0243

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.0593

GnomAD3 exomes AF: 0.0628 AC: 15779 AN: 251452 Hom.: 632 AF XY: 0.0635 AC XY: 8627 AN XY: 135906

Gnomad AFR exome AF: 0.0117

Gnomad AMR exome AF: 0.0396

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.000761

Gnomad SAS exome AF: 0.0288

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.0806

Gnomad OTH exome AF: 0.0701

GnomAD4 exome AF: 0.0671 AC: 98046 AN: 1461784 Hom.: 3733 Cov.: 34 AF XY: 0.0666 AC XY: 48467 AN XY: 727198

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.0414

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.0302

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.0718

Gnomad4 OTH exome AF: 0.0636

GnomAD4 genome AF: 0.0559 AC: 8510 AN: 152282 Hom.: 330 Cov.: 32 AF XY: 0.0576 AC XY: 4290 AN XY: 74460

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0543

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0715 Hom.: 258

Bravo AF: 0.0498

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	5.8
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs34150698; hg19: chr6-37349066;