Genetic Variant RNF186:c.*330G>A (chr1-19814088-C-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_019062.2(RNF186):c.*330G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 267,972 control chromosomes in the GnomAD database, including 1,017 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 0.058 ( 577 hom., cov: 33)

Exomes 𝑓: 0.061 ( 440 hom. )

Consequence

RNF186
NM_019062.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0530

Publications

5 publications found

Variant links:

Genes affected

RNF186 (HGNC:25978): (ring finger protein 186) Enables ubiquitin-protein transferase activity. Involved in several processes, including intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

RNF186 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=-0.59).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF186	NM_019062.2 link	c.*330G>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000375121.4	NP_061935.1	Q9NXI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF186	ENST00000375121.4 link	c.*330G>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_019062.2	ENSP00000364263.2		Q9NXI6

Frequencies

GnomAD3 genomes

AF:

0.0577

AC:

8783

AN:

152202

Hom.:

575

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.0596

Gnomad FIN

AF:

0.0855

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0417

Gnomad OTH

AF:

0.0560

GnomAD4 exome

AF:

0.0608

AC:

7035

AN:

115652

Hom.:

440

Cov.:

AF XY:

0.0610

AC XY:

3554

AN XY:

58266

show subpopulations

African (AFR)

AF:

0.0136

AC:

AN:

4476

American (AMR)

AF:

0.210

AC:

1112

AN:

5298

Ashkenazi Jewish (ASJ)

AF:

0.0309

AC:

125

AN:

4042

East Asian (EAS)

AF:

0.204

AC:

1727

AN:

8464

South Asian (SAS)

AF:

0.0424

AC:

248

AN:

5852

European-Finnish (FIN)

AF:

0.0851

AC:

465

AN:

5466

Middle Eastern (MID)

AF:

0.0231

AC:

AN:

520

European-Non Finnish (NFE)

AF:

0.0384

AC:

2847

AN:

74216

Other (OTH)

AF:

0.0599

AC:

438

AN:

7318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

298

596

894

1192

1490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.0577

AC:

8784

AN:

152320

Hom.:

577

Cov.:

AF XY:

0.0619

AC XY:

4612

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0138

AC:

576

AN:

41594

American (AMR)

AF:

0.184

AC:

2817

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0354

AC:

123

AN:

3470

East Asian (EAS)

AF:

0.211

AC:

1094

AN:

5186

South Asian (SAS)

AF:

0.0580

AC:

280

AN:

4826

European-Finnish (FIN)

AF:

0.0855

AC:

908

AN:

10614

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0417

AC:

2838

AN:

68028

Other (OTH)

AF:

0.0573

AC:

121

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

390

780

1169

1559

1949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0533

Hom.:

768

Bravo

AF:

0.0653

Asia WGS

AF:

0.133

AC:

463

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.8

(source)

DANN

Benign

0.80

PhyloP100

-0.053

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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