6-37366020-C-T

Variant names:

• chr6-37366020-C-T
• rs195385
• NM_003958.4:c.241-2464C>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.241-2464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,938 control chromosomes in the GnomAD database, including 27,055 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 0.58 (27055 hom., cov: 30)
• Consequence: RNF8 NM_003958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 11 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF8	NM_003958.4	c.241-2464C>T		intron_variant	Intron 2 of 7	ENST00000373479.9	NP_003949.1
RNF8	NM_183078.3	c.241-2464C>T		intron_variant	Intron 2 of 6		NP_898901.1
RNF8	NR_046399.2	n.423-2358C>T		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF8	ENST00000373479.9	c.241-2464C>T		intron_variant	Intron 2 of 7	1	NM_003958.4	ENSP00000362578.4

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87524 AN: 151820 Hom.: 27015 Cov.: 30

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.577 AC: 87625 AN: 151938 Hom.: 27055 Cov.: 30 AF XY: 0.578 AC XY: 42901 AN XY: 74228

African (AFR) AF: 0.782 AC: 32406 AN: 41454

American (AMR) AF: 0.577 AC: 8816 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1666 AN: 3466

East Asian (EAS) AF: 0.769 AC: 3970 AN: 5164

South Asian (SAS) AF: 0.654 AC: 3149 AN: 4814

European-Finnish (FIN) AF: 0.385 AC: 4064 AN: 10548

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31817 AN: 67906

Other (OTH) AF: 0.574 AC: 1209 AN: 2108

Alfa AF: 0.486 Hom.: 9438

Bravo AF: 0.598

Asia WGS AF: 0.710 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.4
DANN	Benign	0.42
PhyloP100		1.6
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: rs195385; hg19: chr6-37333796;