rs311778

Variant names:

• chr19-11460472-C-G
• rs311778
• NM_001420.4:c.334-1861G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

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 = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAVL3	NM_001420.4	c.334-1861G>C		intron_variant	Intron 3 of 6	ENST00000359227.8	NP_001411.2
ELAVL3	NM_032281.3	c.334-1861G>C		intron_variant	Intron 3 of 6		NP_115657.2
ELAVL3	XM_011527778.3	c.331-1861G>C		intron_variant	Intron 3 of 6		XP_011526080.1
ELAVL3	XM_024451413.1	c.331-1861G>C		intron_variant	Intron 3 of 6		XP_024307181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAVL3	ENST00000359227.8	c.334-1861G>C		intron_variant	Intron 3 of 6	3	NM_001420.4	ENSP00000352162.1
ELAVL3	ENST00000438662.6	c.334-1861G>C		intron_variant	Intron 3 of 6	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

African (AFR) AF: 0.343 AC: 14207 AN: 41386

American (AMR) AF: 0.0598 AC: 912 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0825 AC: 286 AN: 3468

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5166

South Asian (SAS) AF: 0.0674 AC: 324 AN: 4808

European-Finnish (FIN) AF: 0.0602 AC: 639 AN: 10608

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0579 AC: 3934 AN: 67982

Other (OTH) AF: 0.0977 AC: 206 AN: 2108

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
PhyloP100		0.034
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: rs311778; hg19: chr19-11571287;