Genetic Variant NM_003958.4:c.*2023T>C (chr6-37392781-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003958.4(RNF8):c.*2023T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 397,926 control chromosomes in the GnomAD database, including 10,313 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 0.23 ( 8018 hom., cov: 32)

Exomes 𝑓: 0.094 ( 2295 hom. )

Consequence

RNF8
NM_003958.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.65

Publications

5 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RNF8	NM_003958.4 link	c.*2023T>C	3_prime_UTR_variant	Exon 8 of 8	ENST00000373479.9	NP_003949.1	O76064-1
RNF8	NR_046399.2 link	n.3769T>C	non_coding_transcript_exon_variant	Exon 8 of 8
RNF8	NM_183078.3 link	c.*1929T>C	3_prime_UTR_variant	Exon 7 of 7		NP_898901.1	O76064-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF8	ENST00000373479.9 link	c.*2023T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_003958.4	ENSP00000362578.4		O76064-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34290

AN:

152082

Hom.:

7989

Cov.:

show subpopulations

Gnomad AFR

AF:

0.599

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.0495

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0614

Gnomad OTH

AF:

0.201

GnomAD4 exome

AF:

0.0944

AC:

23188

AN:

245726

Hom.:

2295

Cov.:

AF XY:

0.0922

AC XY:

11477

AN XY:

124526

show subpopulations

African (AFR)

AF:

0.590

AC:

4236

AN:

7178

American (AMR)

AF:

0.171

AC:

1272

AN:

7432

Ashkenazi Jewish (ASJ)

AF:

0.0966

AC:

892

AN:

9236

East Asian (EAS)

AF:

0.154

AC:

3513

AN:

22846

South Asian (SAS)

AF:

0.131

AC:

346

AN:

2644

European-Finnish (FIN)

AF:

0.0472

AC:

982

AN:

20800

Middle Eastern (MID)

AF:

0.121

AC:

156

AN:

1294

European-Non Finnish (NFE)

AF:

0.0610

AC:

9640

AN:

157938

Other (OTH)

AF:

0.131

AC:

2151

AN:

16358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1038

2076

3113

4151

5189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.226

AC:

34367

AN:

152200

Hom.:

8018

Cov.:

AF XY:

0.221

AC XY:

16477

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.599

AC:

24854

AN:

41486

American (AMR)

AF:

0.173

AC:

2653

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

367

AN:

3470

East Asian (EAS)

AF:

0.119

AC:

619

AN:

5190

South Asian (SAS)

AF:

0.141

AC:

679

AN:

4820

European-Finnish (FIN)

AF:

0.0495

AC:

524

AN:

10596

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0614

AC:

4178

AN:

68022

Other (OTH)

AF:

0.199

AC:

422

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

971

1942

2912

3883

4854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.106

Hom.:

4177

Bravo

AF:

0.253

Asia WGS

AF:

0.170

AC:

592

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.29

(source)

DANN

Benign

0.56

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over