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GeneBe

6-37360582-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003958.4(RNF8):c.240+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,610,674 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

RNF8
NM_003958.4 splice_region, intron

Scores

2
Splicing: ADA: 0.0001789
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.993
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 6-37360582-A-G is Benign according to our data. Variant chr6-37360582-A-G is described in ClinVar as [Benign]. Clinvar id is 780620.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF8NM_003958.4 linkuse as main transcriptc.240+8A>G splice_region_variant, intron_variant ENST00000373479.9
RNF8NM_183078.3 linkuse as main transcriptc.240+8A>G splice_region_variant, intron_variant
RNF8NR_046399.2 linkuse as main transcriptn.422+8A>G splice_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF8ENST00000373479.9 linkuse as main transcriptc.240+8A>G splice_region_variant, intron_variant 1 NM_003958.4 P1O76064-1

Frequencies

GnomAD3 genomes
AF:
0.00191
AC:
291
AN:
152084
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00657
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000514
AC:
128
AN:
249266
Hom.:
0
AF XY:
0.000305
AC XY:
41
AN XY:
134604
show subpopulations
Gnomad AFR exome
AF:
0.00648
Gnomad AMR exome
AF:
0.000583
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000335
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000886
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000149
AC:
218
AN:
1458474
Hom.:
1
Cov.:
31
AF XY:
0.000126
AC XY:
91
AN XY:
725078
show subpopulations
Gnomad4 AFR exome
AF:
0.00512
Gnomad4 AMR exome
AF:
0.000516
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000584
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000266
GnomAD4 genome
AF:
0.00192
AC:
292
AN:
152200
Hom.:
2
Cov.:
32
AF XY:
0.00187
AC XY:
139
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.00658
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00104
Hom.:
0
Bravo
AF:
0.00220

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
5.8
Dann
Benign
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00018
dbscSNV1_RF
Benign
0.0040
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.

Other links and lift over

dbSNP: rs370830769; hg19: chr6-37328358; API