rs195382

Positions:

• chr6-37370573-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.976-939A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,104 control chromosomes in the GnomAD database, including 4,090 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 0.13 (4090 hom., cov: 32)
• Consequence: RNF8 NM_003958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF8	NM_003958.4	c.976-939A>T		intron_variant		ENST00000373479.9	NP_003949.1
RNF8	NM_183078.3	c.976-939A>T		intron_variant			NP_898901.1
RNF8	NR_046399.2	n.1264-939A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF8	ENST00000373479.9	c.976-939A>T		intron_variant		1	NM_003958.4	ENSP00000362578	P1
RNF8	ENST00000469731.5	c.976-939A>T		intron_variant		5		ENSP00000418879
RNF8	ENST00000498460.1	c.344-939A>T		intron_variant		3		ENSP00000417599
RNF8	ENST00000229866.10	c.*785-939A>T		intron_variant, NMD_transcript_variant		2		ENSP00000229866

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20373 AN: 151986 Hom.: 4071 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.0358

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00472

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.134 AC: 20436 AN: 152104 Hom.: 4090 Cov.: 32 AF XY: 0.132 AC XY: 9818 AN XY: 74366

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.0668

Gnomad4 ASJ AF: 0.0358

Gnomad4 EAS AF: 0.0895

Gnomad4 SAS AF: 0.0527

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00472

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0801 Hom.: 307

Bravo AF: 0.154

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.43

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: rs195382; hg19: chr6-37338349;