8-100270857-C-T

Variant names:

• chr8-100270857-C-T
• rs7837658
• NM_183419.4:c.884-844G>A

Variant summary

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

The NM_183419.4(RNF19A):​c.884-844G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,050 control chromosomes in the GnomAD database, including 4,004 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 0.13 (4004 hom., cov: 32)
• Consequence: RNF19A NM_183419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.481
• Publications: 2 publications found

Genes affected

RNF19A (HGNC:13432): (ring finger protein 19A, RBR E3 ubiquitin protein ligase) This gene encodes a member of the ring between ring fingers (RBR) protein family, and the encoded protein contains two RING-finger motifs and an in between RING fingers motif. This protein is an E3 ubiquitin ligase that is localized to Lewy bodies, and ubiquitylates synphilin-1, which is an interacting protein of alpha synuclein in neurons. The encoded protein may be involved in amyotrophic lateral sclerosis and Parkinson's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183419.4. 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
	RNF19A	NM_183419.4	MANE Select	c.884-844G>A		intron	N/A	NP_904355.1
	RNF19A	NM_001280539.2		c.884-844G>A		intron	N/A	NP_001267468.1
	RNF19A	NM_001353837.2		c.884-844G>A		intron	N/A	NP_001340766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF19A	ENST00000341084.7	TSL:5 MANE Select	c.884-844G>A		intron	N/A	ENSP00000342667.2
	RNF19A	ENST00000519449.5	TSL:1	c.884-844G>A		intron	N/A	ENSP00000428968.1
	RNF19A	ENST00000524233.1	TSL:3	n.83-844G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19931 AN: 151932 Hom.: 3996 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0697

Gnomad SAS AF: 0.0598

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.00290

Gnomad OTH AF: 0.101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.131 AC: 19976 AN: 152050 Hom.: 4004 Cov.: 32 AF XY: 0.128 AC XY: 9504 AN XY: 74334

African (AFR) AF: 0.433 AC: 17926 AN: 41442

American (AMR) AF: 0.0620 AC: 948 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.0697 AC: 361 AN: 5182

South Asian (SAS) AF: 0.0597 AC: 288 AN: 4826

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.00290 AC: 197 AN: 67914

Other (OTH) AF: 0.102 AC: 214 AN: 2108

Alfa AF: 0.0539 Hom.: 3893

Bravo AF: 0.148

Asia WGS AF: 0.0920 AC: 319 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.37
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7837658; hg19: chr8-101283085;