Variant 6-37381144-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003958.4(RNF8):c.1237-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,610,168 control chromosomes in the GnomAD database, including 198,017 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 20883 hom., cov: 32)

Exomes 𝑓: 0.49 ( 177134 hom. )

Consequence

RNF8
NM_003958.4 splice_region, intron

Scores

Splicing: ADA: 0.00002030

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.247

Variant links:

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]

RNF8 links:

RNF8 (HGNC:):

RNF8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RNF8	NM_003958.4 linkuse as main transcript	c.1237-6C>T	splice_region_variant, intron_variant	ENST00000373479.9	NP_003949.1	O76064-1
RNF8	NM_183078.3 linkuse as main transcript	c.1236+4111C>T	intron_variant		NP_898901.1	O76064-3
RNF8	NR_046399.2 linkuse as main transcript	n.1525-6C>T	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RNF8	ENST00000373479.9 linkuse as main transcript	c.1237-6C>T	splice_region_variant, intron_variant	1	NM_003958.4	ENSP00000362578.4	O76064-1
RNF8	ENST00000469731.5 linkuse as main transcript	c.1236+4111C>T	intron_variant	5		ENSP00000418879.1	O76064-3
RNF8	ENST00000498460.1 linkuse as main transcript	c.513+4111C>T	intron_variant	3		ENSP00000417599.1	H7C4L7
RNF8	ENST00000229866.10 linkuse as main transcript	n.*1046-6C>T	splice_region_variant, intron_variant	2		ENSP00000229866.6	O76064-2

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78298

AN:

151942

Hom.:

20842

Cov.:

show subpopulations

Gnomad AFR

AF:

0.582

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.766

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.514

GnomAD3 exomes

AF:

0.519

AC:

130531

AN:

251296

Hom.:

35402

AF XY:

0.518

AC XY:

70386

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.580

Gnomad AMR exome

AF:

0.574

Gnomad ASJ exome

AF:

0.473

Gnomad EAS exome

AF:

0.769

Gnomad SAS exome

AF:

0.622

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.458

Gnomad OTH exome

AF:

0.491

GnomAD4 exome

AF:

0.486

AC:

709058

AN:

1458108

Hom.:

177134

Cov.:

AF XY:

0.489

AC XY:

355086

AN XY:

725584

show subpopulations

Gnomad4 AFR exome

AF:

0.583

Gnomad4 AMR exome

AF:

0.568

Gnomad4 ASJ exome

AF:

0.468

Gnomad4 EAS exome

AF:

0.792

Gnomad4 SAS exome

AF:

0.623

Gnomad4 FIN exome

AF:

0.382

Gnomad4 NFE exome

AF:

0.463

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.516

AC:

78391

AN:

152060

Hom.:

20883

Cov.:

AF XY:

0.518

AC XY:

38529

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.582

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.766

Gnomad4 SAS

AF:

0.638

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.466

Gnomad4 OTH

AF:

0.518

Alfa

AF:

0.477

Hom.:

42474

Bravo

AF:

0.529

Asia WGS

AF:

0.688

AC:

2394

AN:

3478

EpiCase

AF:

0.454

EpiControl

AF:

0.458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.96

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over