dbSNP rs2284922: RNF8:p.Thr448Thr (chr6-37381257-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003958.4(RNF8):c.1344G>A(p.Thr448Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,613,596 control chromosomes in the GnomAD database, including 126,926 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 0.43 ( 14981 hom., cov: 32)

Exomes 𝑓: 0.38 ( 111945 hom. )

Consequence

RNF8
NM_003958.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.954

Publications

29 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-0.954 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF8	NM_003958.4 link	c.1344G>A	p.Thr448Thr	synonymous_variant	Exon 7 of 8	ENST00000373479.9	NP_003949.1	O76064-1
RNF8	NR_046399.2 link	n.1632G>A		non_coding_transcript_exon_variant	Exon 7 of 8
RNF8	NM_183078.3 link	c.1236+4224G>A		intron_variant	Intron 6 of 6		NP_898901.1	O76064-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF8	ENST00000373479.9 link	c.1344G>A	p.Thr448Thr	synonymous_variant	Exon 7 of 8	1	NM_003958.4	ENSP00000362578.4		O76064-1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

65060

AN:

151844

Hom.:

14947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.531

Gnomad AMI

AF:

0.217

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.740

Gnomad SAS

AF:

0.603

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.451

GnomAD2 exomes

AF:

0.441

AC:

110920

AN:

251466

AF XY:

0.439

show subpopulations

Gnomad AFR exome

AF:

0.533

Gnomad AMR exome

AF:

0.538

Gnomad ASJ exome

AF:

0.435

Gnomad EAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.290

Gnomad NFE exome

AF:

0.342

Gnomad OTH exome

AF:

0.408

GnomAD4 exome

AF:

0.377

AC:

551012

AN:

1461634

Hom.:

111945

Cov.:

AF XY:

0.382

AC XY:

278030

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.540

AC:

18084

AN:

33468

American (AMR)

AF:

0.529

AC:

23669

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.429

AC:

11209

AN:

26134

East Asian (EAS)

AF:

0.768

AC:

30494

AN:

39698

South Asian (SAS)

AF:

0.584

AC:

50388

AN:

86250

European-Finnish (FIN)

AF:

0.286

AC:

15299

AN:

53420

Middle Eastern (MID)

AF:

0.434

AC:

2501

AN:

5768

European-Non Finnish (NFE)

AF:

0.337

AC:

374776

AN:

1111784

Other (OTH)

AF:

0.407

AC:

24592

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

17835

35669

53504

71338

89173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12414

24828

37242

49656

62070

<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:

0.429

AC:

65155

AN:

151962

Hom.:

14981

Cov.:

AF XY:

0.434

AC XY:

32242

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.532

AC:

22041

AN:

41438

American (AMR)

AF:

0.485

AC:

7407

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

1502

AN:

3470

East Asian (EAS)

AF:

0.739

AC:

3812

AN:

5156

South Asian (SAS)

AF:

0.603

AC:

2907

AN:

4824

European-Finnish (FIN)

AF:

0.287

AC:

3025

AN:

10542

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.341

AC:

23173

AN:

67948

Other (OTH)

AF:

0.457

AC:

965

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1813

3626

5440

7253

9066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<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:

0.376

Hom.:

22075

Bravo

AF:

0.446

Asia WGS

AF:

0.660

AC:

2297

AN:

3478

EpiCase

AF:

0.344

EpiControl

AF:

0.348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.6

(source)

DANN

Benign

0.58

PhyloP100

-0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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