chr8-100282771-G-C

Variant names:

• chr8-100282771-G-C
• rs7836072
• NM_183419.4:c.674+4730C>G

Variant summary

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

The NM_183419.4(RNF19A):​c.674+4730C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,164 control chromosomes in the GnomAD database, including 4,022 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 (4022 hom., cov: 32)
• Consequence: RNF19A NM_183419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 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.674+4730C>G		intron	N/A	NP_904355.1
	RNF19A	NM_001280539.2		c.674+4730C>G		intron	N/A	NP_001267468.1
	RNF19A	NM_001353837.2		c.674+4730C>G		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.674+4730C>G		intron	N/A	ENSP00000342667.2
	RNF19A	ENST00000519449.5	TSL:1	c.674+4730C>G		intron	N/A	ENSP00000428968.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19972 AN: 152046 Hom.: 4014 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0622

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0699

Gnomad SAS AF: 0.0594

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.00287

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.132 AC: 20017 AN: 152164 Hom.: 4022 Cov.: 32 AF XY: 0.128 AC XY: 9532 AN XY: 74412

African (AFR) AF: 0.433 AC: 17966 AN: 41452

American (AMR) AF: 0.0621 AC: 949 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.0698 AC: 362 AN: 5184

South Asian (SAS) AF: 0.0593 AC: 286 AN: 4826

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00287 AC: 195 AN: 68022

Other (OTH) AF: 0.103 AC: 217 AN: 2112

Alfa AF: 0.0762 Hom.: 284

Bravo AF: 0.149

Asia WGS AF: 0.0920 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.61
PhyloP100		-0.53
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: rs7836072; hg19: chr8-101294999;