rs311778

Positions:

• chr19-11460472-C-G

Variant summary

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

The NM_001420.4(ELAVL3):​c.334-1861G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 151,980 control chromosomes in the GnomAD database, including 2,687 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 0.14 (2687 hom., cov: 29)
• Consequence: ELAVL3 NM_001420.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

Genes affected

ELAVL3 (HGNC:3314): (ELAV like RNA binding protein 3) A member of the ELAVL protein family, ELAV-like 3 is a neural-specific RNA-binding protein which contains three RNP-type RNA recognition motifs. The observation that ELAVL3 is one of several Hu antigens (neuronal-specific RNA-binding proteins) recognized by the anti-Hu serum antibody present in sera from patients with paraneoplastic encephalomyelitis and sensory neuronopathy (PEM/PSN) suggests it has a role in neurogenesis. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -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 = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAVL3	NM_001420.4	c.334-1861G>C		intron_variant		ENST00000359227.8	NP_001411.2
ELAVL3	NM_032281.3	c.334-1861G>C		intron_variant			NP_115657.2
ELAVL3	XM_011527778.3	c.331-1861G>C		intron_variant			XP_011526080.1
ELAVL3	XM_024451413.1	c.331-1861G>C		intron_variant			XP_024307181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAVL3	ENST00000359227.8	c.334-1861G>C		intron_variant		3	NM_001420.4	ENSP00000352162.1
ELAVL3	ENST00000438662.6	c.334-1861G>C		intron_variant		5		ENSP00000390878.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20522 AN: 151862 Hom.: 2682 Cov.: 29

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0579

Gnomad OTH AF: 0.0988

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

GnomAD4 genome AF: 0.135 AC: 20548 AN: 151980 Hom.: 2687 Cov.: 29 AF XY: 0.133 AC XY: 9855 AN XY: 74284

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.0598

Gnomad4 ASJ AF: 0.0825

Gnomad4 EAS AF: 0.000968

Gnomad4 SAS AF: 0.0674

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.0579

Gnomad4 OTH AF: 0.0977

Alfa AF: 0.117 Hom.: 250

Bravo AF: 0.142

Asia WGS AF: 0.0550 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.56

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: rs311778; hg19: chr19-11571287;