rs195432

Variant names:

• chr6-37390246-A-C
• rs195432
• NM_003958.4:c.1442-496A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-37390246-A-C
• chr6-37390246-A-G
• chr6-37390246-A-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.1442-496A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,198 control chromosomes in the GnomAD database, including 43,955 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 0.75 (43955 hom., cov: 33)
• Consequence: RNF8 NM_003958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 7 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF8	NM_003958.4	c.1442-496A>C		intron_variant	Intron 7 of 7	ENST00000373479.9	NP_003949.1
RNF8	NM_183078.3	c.1237-496A>C		intron_variant	Intron 6 of 6		NP_898901.1
RNF8	NR_046399.2	n.1730-496A>C		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF8	ENST00000373479.9	c.1442-496A>C		intron_variant	Intron 7 of 7	1	NM_003958.4	ENSP00000362578.4
RNF8	ENST00000469731.5	c.1237-496A>C		intron_variant	Intron 6 of 6	5		ENSP00000418879.1
RNF8	ENST00000498460.1	c.514-496A>C		intron_variant	Intron 3 of 3	3		ENSP00000417599.1
RNF8	ENST00000229866.10	n.*1251-496A>C		intron_variant	Intron 7 of 7	2		ENSP00000229866.6

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113701 AN: 152080 Hom.: 43894 Cov.: 33

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.748 AC: 113825 AN: 152198 Hom.: 43955 Cov.: 33 AF XY: 0.752 AC XY: 55919 AN XY: 74390

African (AFR) AF: 0.936 AC: 38885 AN: 41540

American (AMR) AF: 0.735 AC: 11232 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2137 AN: 3468

East Asian (EAS) AF: 0.918 AC: 4757 AN: 5180

South Asian (SAS) AF: 0.780 AC: 3758 AN: 4820

European-Finnish (FIN) AF: 0.684 AC: 7234 AN: 10580

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43639 AN: 68004

Other (OTH) AF: 0.730 AC: 1543 AN: 2114

Alfa AF: 0.674 Hom.: 44868

Bravo AF: 0.760

Asia WGS AF: 0.863 AC: 3001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.29
DANN	Benign	0.47
PhyloP100		-1.0
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: rs195432; hg19: chr6-37358022;