rs4714059

Positions:

• chr6-37354015-G-T

Variant summary

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

The NM_003958.4(RNF8):​c.-150G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 713,046 control chromosomes in the GnomAD database, including 1,911 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 0.057 (318 hom., cov: 32)
  • Exomes 𝑓: 0.071 (1593 hom.)
• Consequence: RNF8 NM_003958.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75

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=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF8	NM_003958.4	c.-150G>T		5_prime_UTR_variant	1/8	ENST00000373479.9	NP_003949.1
RNF8	NM_183078.3	c.-150G>T		5_prime_UTR_variant	1/7		NP_898901.1
RNF8	NR_046399.2	n.33G>T		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF8	ENST00000373479.9	c.-150G>T		5_prime_UTR_variant	1/8	1	NM_003958.4	ENSP00000362578	P1
RNF8	ENST00000229866.10	c.-150G>T		5_prime_UTR_variant, NMD_transcript_variant	1/8	2		ENSP00000229866
RNF8	ENST00000494320.5	c.-150G>T		5_prime_UTR_variant, NMD_transcript_variant	1/4	5		ENSP00000420268
RNF8	ENST00000487950.1			upstream_gene_variant		4		ENSP00000417736

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8701 AN: 152210 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.0364

Gnomad SAS AF: 0.0868

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0670

GnomAD4 exome AF: 0.0709 AC: 39750 AN: 560718 Hom.: 1593 Cov.: 8 AF XY: 0.0724 AC XY: 21204 AN XY: 292918

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.0647

Gnomad4 EAS exome AF: 0.0202

Gnomad4 SAS exome AF: 0.0934

Gnomad4 FIN exome AF: 0.0663

Gnomad4 NFE exome AF: 0.0707

Gnomad4 OTH exome AF: 0.0667

GnomAD4 genome AF: 0.0571 AC: 8694 AN: 152328 Hom.: 318 Cov.: 32 AF XY: 0.0576 AC XY: 4291 AN XY: 74486

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.0968

Gnomad4 ASJ AF: 0.0704

Gnomad4 EAS AF: 0.0365

Gnomad4 SAS AF: 0.0863

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.0708

Gnomad4 OTH AF: 0.0663

Alfa AF: 0.0641 Hom.: 46

Bravo AF: 0.0584

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.6
DANN	Benign	0.93
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

Publications

LitVar

Other links and lift over

dbSNP: rs4714059; hg19: chr6-37321791;