rs104669

Variant names:

• chr6-37386283-A-T
• rs104669
• NM_003958.4:c.1442-4459A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.97).
• 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 rank	MANE	Protein	UniProt
RNF8	NM_003958.4	c.1442-4459A>T		intron_variant	Intron 7 of 7	ENST00000373479.9	NP_003949.1
RNF8	NM_183078.3	c.1237-4459A>T		intron_variant	Intron 6 of 6		NP_898901.1
RNF8	NR_046399.2	n.1730-4459A>T		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF8	ENST00000373479.9	c.1442-4459A>T		intron_variant	Intron 7 of 7	1	NM_003958.4	ENSP00000362578.4
RNF8	ENST00000469731.5	c.1237-4459A>T		intron_variant	Intron 6 of 6	5		ENSP00000418879.1
RNF8	ENST00000498460.1	c.514-4459A>T		intron_variant	Intron 3 of 3	3		ENSP00000417599.1
RNF8	ENST00000229866.10	n.*1251-4459A>T		intron_variant	Intron 7 of 7	2		ENSP00000229866.6

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

African (AFR) AF: 0.740 AC: 30664 AN: 41412

American (AMR) AF: 0.562 AC: 8562 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1587 AN: 3464

East Asian (EAS) AF: 0.813 AC: 4207 AN: 5172

South Asian (SAS) AF: 0.625 AC: 3011 AN: 4816

European-Finnish (FIN) AF: 0.372 AC: 3908 AN: 10498

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.346 AC: 23310 AN: 67412

Other (OTH) AF: 0.514 AC: 1077 AN: 2096

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
PhyloP100		-0.60
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: rs104669; hg19: chr6-37354059;