rs1371867

chr8-100317981-A-Cchr8-100317981-A-Gchr8-100317981-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001280539.2(RNF19A):c.-175-4609T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,594 control chromosomes in the GnomAD database, including 22,055 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 0.52 (22055 hom., cov: 30)
• Consequence: RNF19A NM_001280539.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF19A	NM_001280539.2	c.-175-4609T>G		intron_variant
RNF19A	XM_047421664.1	c.-2719-4609T>G		intron_variant
RNF19A	XM_047421665.1	c.-3085-4609T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF19A	ENST00000519527.5	c.-242-4609T>G		intron_variant		3
RNF19A	ENST00000522369.5	c.-175-4609T>G		intron_variant		4
RNF19A	ENST00000522182.1	n.112-4609T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.521 AC: 78916 AN: 151474 Hom.: 22015 Cov.: 30

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.521 AC: 79015 AN: 151594 Hom.: 22055 Cov.: 30 AF XY: 0.517 AC XY: 38270 AN XY: 74060

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.505

Alfa AF: 0.445 Hom.: 22840

Bravo AF: 0.530

Asia WGS AF: 0.535 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.8
Dann	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs1371867; hg19: chr8-101330209;