1-19814088-C-T

Variant names:

• chr1-19814088-C-T
• rs3820317
• NM_019062.2:c.*330G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 5 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019062.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF186	NM_019062.2	MANE Select	c.*330G>A		3_prime_UTR	Exon 1 of 1	NP_061935.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF186	ENST00000375121.4	TSL:6 MANE Select	c.*330G>A		3_prime_UTR	Exon 1 of 1	ENSP00000364263.2

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8783 AN: 152202 Hom.: 575 Cov.: 33

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.: 0 AF XY: 0.0610 AC XY: 3554 AN XY: 58266

African (AFR) AF: 0.0136 AC: 61 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: 12 AN: 520

European-Non Finnish (NFE) AF: 0.0384 AC: 2847 AN: 74216

Other (OTH) AF: 0.0599 AC: 438 AN: 7318

GnomAD4 genome AF: 0.0577 AC: 8784 AN: 152320 Hom.: 577 Cov.: 33 AF XY: 0.0619 AC XY: 4612 AN XY: 74480

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: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0417 AC: 2838 AN: 68028

Other (OTH) AF: 0.0573 AC: 121 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.8
DANN	Benign	0.80
PhyloP100		-0.053
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3820317; hg19: chr1-20140581; COSMIC: COSV107497499; COSMIC: COSV107497499;