rs104669

Positions:

• chr6-37386283-A-T

Variant summary

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

The NM_003958.4(RNF8):​c.1442-4459A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,300 control chromosomes in the GnomAD database, including 21,885 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 0.51 (21885 hom., cov: 31)
• Consequence: RNF8 NM_003958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF8	NM_003958.4	c.1442-4459A>T		intron_variant		ENST00000373479.9
RNF8	NM_183078.3	c.1237-4459A>T		intron_variant
RNF8	NR_046399.2	n.1730-4459A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF8	ENST00000373479.9	c.1442-4459A>T		intron_variant		1	NM_003958.4	P1
RNF8	ENST00000469731.5	c.1237-4459A>T		intron_variant		5
RNF8	ENST00000498460.1	c.515-4459A>T		intron_variant		3
RNF8	ENST00000229866.10	c.*1251-4459A>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76563 AN: 151180 Hom.: 21835 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.509

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.507 AC: 76677 AN: 151300 Hom.: 21885 Cov.: 31 AF XY: 0.514 AC XY: 38021 AN XY: 73986

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.514

Alfa AF: 0.424 Hom.: 2044

Bravo AF: 0.530

Asia WGS AF: 0.728 AC: 2533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.79

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: rs104669; hg19: chr6-37354059;