Genetic Variant RNF8:c.-150G>T (chr6-37354015-G-T) – 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.-150G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 713,046 control chromosomes in the GnomAD database, including 1,911 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 0.057 ( 318 hom., cov: 32)

Exomes 𝑓: 0.071 ( 1593 hom. )

Consequence

RNF8
NM_003958.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.75

Publications

4 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:

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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=-0.69).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RNF8	NM_003958.4 link	c.-150G>T	5_prime_UTR_variant	Exon 1 of 8	ENST00000373479.9	NP_003949.1	O76064-1
RNF8	NR_046399.2 link	n.33G>T	non_coding_transcript_exon_variant	Exon 1 of 8
RNF8	NM_183078.3 link	c.-150G>T	5_prime_UTR_variant	Exon 1 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.-150G>T		5_prime_UTR_variant	Exon 1 of 8	1	NM_003958.4	ENSP00000362578.4		O76064-1

Frequencies

GnomAD3 genomes

AF:

0.0572

AC:

8701

AN:

152210

Hom.:

319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.0945

Gnomad AMR

AF:

0.0971

Gnomad ASJ

AF:

0.0704

Gnomad EAS

AF:

0.0364

Gnomad SAS

AF:

0.0868

Gnomad FIN

AF:

0.0678

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0707

Gnomad OTH

AF:

0.0670

GnomAD4 exome

AF:

0.0709

AC:

39750

AN:

560718

Hom.:

1593

Cov.:

AF XY:

0.0724

AC XY:

21204

AN XY:

292918

show subpopulations

African (AFR)

AF:

0.0148

AC:

212

AN:

14286

American (AMR)

AF:

0.131

AC:

3433

AN:

26256

Ashkenazi Jewish (ASJ)

AF:

0.0647

AC:

1032

AN:

15950

East Asian (EAS)

AF:

0.0202

AC:

599

AN:

29726

South Asian (SAS)

AF:

0.0934

AC:

5049

AN:

54048

European-Finnish (FIN)

AF:

0.0663

AC:

2341

AN:

35306

Middle Eastern (MID)

AF:

0.0538

AC:

127

AN:

2360

European-Non Finnish (NFE)

AF:

0.0707

AC:

24979

AN:

353136

Other (OTH)

AF:

0.0667

AC:

1978

AN:

29650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

2087

4175

6262

8350

10437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.0571

AC:

8694

AN:

152328

Hom.:

318

Cov.:

AF XY:

0.0576

AC XY:

4291

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0141

AC:

586

AN:

41580

American (AMR)

AF:

0.0968

AC:

1482

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0704

AC:

244

AN:

3468

East Asian (EAS)

AF:

0.0365

AC:

189

AN:

5182

South Asian (SAS)

AF:

0.0863

AC:

417

AN:

4832

European-Finnish (FIN)

AF:

0.0678

AC:

720

AN:

10616

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0708

AC:

4814

AN:

68028

Other (OTH)

AF:

0.0663

AC:

140

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

460

921

1381

1842

2302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0641

Hom.:

Bravo

AF:

0.0584

Asia WGS

AF:

0.0770

AC:

268

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.6

(source)

DANN

Benign

0.93

PhyloP100

-2.8

PromoterAI

0.062

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

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