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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003958.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RNF8	NM_003958.4	MANE Select	c.-150G>T	5_prime_UTR	Exon 1 of 8	NP_003949.1	O76064-1
RNF8	NM_183078.3		c.-150G>T	5_prime_UTR	Exon 1 of 7	NP_898901.1	O76064-3
RNF8	NR_046399.2		n.33G>T	non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RNF8	ENST00000373479.9	TSL:1 MANE Select	c.-150G>T	5_prime_UTR	Exon 1 of 8	ENSP00000362578.4	O76064-1
RNF8	ENST00000918865.1		c.-150G>T	5_prime_UTR	Exon 1 of 8	ENSP00000588924.1
RNF8	ENST00000918866.1		c.-150G>T	5_prime_UTR	Exon 1 of 8	ENSP00000588925.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over