19-11466211-G-A

Position:

• chr19-11466211-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001420.4(ELAVL3):​c.294C>T​(p.Asn98Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.00171 in 1,613,864 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (20 hom., cov: 31)
  • Exomes 𝑓: 0.00099 (27 hom.)
• Consequence: ELAVL3 NM_001420.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.39

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 19-11466211-G-A is Benign according to our data. Variant chr19-11466211-G-A is described in ClinVar as [Benign]. Clinvar id is 716500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00869 (1322/152154) while in subpopulation AFR AF= 0.0304 (1262/41482). AF 95% confidence interval is 0.029. There are 20 homozygotes in gnomad4. There are 635 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1322 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAVL3	NM_001420.4	c.294C>T	p.Asn98Asn	synonymous_variant	3/7	ENST00000359227.8	NP_001411.2
ELAVL3	NM_032281.3	c.294C>T	p.Asn98Asn	synonymous_variant	3/7		NP_115657.2
ELAVL3	XM_011527778.3	c.291C>T	p.Asn97Asn	synonymous_variant	3/7		XP_011526080.1
ELAVL3	XM_024451413.1	c.291C>T	p.Asn97Asn	synonymous_variant	3/7		XP_024307181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAVL3	ENST00000359227.8	c.294C>T	p.Asn98Asn	synonymous_variant	3/7	3	NM_001420.4	ENSP00000352162.1
ELAVL3	ENST00000438662.6	c.294C>T	p.Asn98Asn	synonymous_variant	3/7	5		ENSP00000390878.1
ELAVL3	ENST00000588853.1	c.243C>T	p.Asn81Asn	synonymous_variant	3/3	3		ENSP00000467314.1
ENSG00000267477	ENST00000585656.1	n.*190C>T		downstream_gene_variant		5		ENSP00000466387.1

Frequencies

GnomAD3 genomes AF: 0.00866 AC: 1316 AN: 152036 Hom.: 20 Cov.: 31

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

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: 0.0000882

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.00241 AC: 606 AN: 251374 Hom.: 13 AF XY: 0.00175 AC XY: 238 AN XY: 135846

Gnomad AFR exome AF: 0.0311

Gnomad AMR exome AF: 0.00188

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: 0.000299

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000987 AC: 1442 AN: 1461710 Hom.: 27 Cov.: 32 AF XY: 0.000869 AC XY: 632 AN XY: 727158

Gnomad4 AFR exome AF: 0.0306

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000169

Gnomad4 OTH exome AF: 0.00200

GnomAD4 genome AF: 0.00869 AC: 1322 AN: 152154 Hom.: 20 Cov.: 31 AF XY: 0.00854 AC XY: 635 AN XY: 74392

Gnomad4 AFR AF: 0.0304

Gnomad4 AMR AF: 0.00236

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00424 Hom.: 5

Bravo AF: 0.00937

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000534

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.1
DANN	Benign	0.80

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: rs61741718; hg19: chr19-11577026;