19-11466783-G-A

Position:

• chr19-11466783-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The NM_001420.4(ELAVL3):​c.54C>T​(p.Ala18Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,613,262 control chromosomes in the GnomAD database, including 55 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (23 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (32 hom.)
• Consequence: ELAVL3 NM_001420.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.89

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]

ENSG00000267477 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP6: Variant 19-11466783-G-A is Benign according to our data. Variant chr19-11466783-G-A is described in ClinVar as [Benign]. Clinvar id is 716501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.89 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1543/152234) while in subpopulation AFR AF= 0.0356 (1477/41546). AF 95% confidence interval is 0.034. There are 23 homozygotes in gnomad4. There are 726 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1543 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAVL3	NM_001420.4	c.54C>T	p.Ala18Ala	synonymous_variant	2/7	ENST00000359227.8	NP_001411.2
ELAVL3	NM_032281.3	c.54C>T	p.Ala18Ala	synonymous_variant	2/7		NP_115657.2
ELAVL3	XM_011527778.3	c.51C>T	p.Ala17Ala	synonymous_variant	2/7		XP_011526080.1
ELAVL3	XM_024451413.1	c.51C>T	p.Ala17Ala	synonymous_variant	2/7		XP_024307181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAVL3	ENST00000359227.8	c.54C>T	p.Ala18Ala	synonymous_variant	2/7	3	NM_001420.4	ENSP00000352162.1
ENSG00000267477	ENST00000585656.1	n.514C>T		non_coding_transcript_exon_variant	4/5	5		ENSP00000466387.1
ELAVL3	ENST00000438662.6	c.54C>T	p.Ala18Ala	synonymous_variant	2/7	5		ENSP00000390878.1
ELAVL3	ENST00000588853.1	c.54C>T	p.Ala18Ala	synonymous_variant	2/3	3		ENSP00000467314.1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1537 AN: 152116 Hom.: 23 Cov.: 31

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00282 AC: 695 AN: 246780 Hom.: 16 AF XY: 0.00211 AC XY: 282 AN XY: 133828

Gnomad AFR exome AF: 0.0370

Gnomad AMR exome AF: 0.00199

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000370

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.00112 AC: 1643 AN: 1461028 Hom.: 32 Cov.: 33 AF XY: 0.000991 AC XY: 720 AN XY: 726792

Gnomad4 AFR exome AF: 0.0354

Gnomad4 AMR exome AF: 0.00200

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000183

Gnomad4 OTH exome AF: 0.00230

GnomAD4 genome AF: 0.0101 AC: 1543 AN: 152234 Hom.: 23 Cov.: 31 AF XY: 0.00975 AC XY: 726 AN XY: 74434

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00338 Hom.: 3

Bravo AF: 0.0109

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	0.030
CADD	Benign	14
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs62000391; hg19: chr19-11577598; COSMIC: COSV63645783;