Genetic Variant ELAVL3:c.714-59T>A (chr19-11457207-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001420.4(ELAVL3):c.714-59T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 1,501,680 control chromosomes in the GnomAD database, including 6,250 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 0.13 ( 2537 hom., cov: 29)

Exomes 𝑓: 0.056 ( 3713 hom. )

Consequence

ELAVL3
NM_001420.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.506

Publications

4 publications found

Variant links:

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]

ELAVL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001420.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAVL3	NM_001420.4	MANE Select	c.714-59T>A		intron	N/A	NP_001411.2
	ELAVL3	NM_032281.3		c.714-59T>A		intron	N/A	NP_115657.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAVL3	ENST00000359227.8	TSL:3 MANE Select	c.714-59T>A		intron	N/A	ENSP00000352162.1
	ELAVL3	ENST00000438662.6	TSL:5	c.714-59T>A		intron	N/A	ENSP00000390878.1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19628

AN:

150508

Hom.:

2532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0591

Gnomad ASJ

AF:

0.0829

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.0666

Gnomad FIN

AF:

0.0560

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.0982

GnomAD4 exome

AF:

0.0563

AC:

76089

AN:

1351060

Hom.:

3713

AF XY:

0.0566

AC XY:

37726

AN XY:

666464

show subpopulations

African (AFR)

AF:

0.346

AC:

9698

AN:

28016

American (AMR)

AF:

0.0328

AC:

938

AN:

28566

Ashkenazi Jewish (ASJ)

AF:

0.0813

AC:

1925

AN:

23664

East Asian (EAS)

AF:

0.000340

AC:

AN:

32388

South Asian (SAS)

AF:

0.0676

AC:

4892

AN:

72412

European-Finnish (FIN)

AF:

0.0610

AC:

2989

AN:

49032

Middle Eastern (MID)

AF:

0.0881

AC:

353

AN:

4008

European-Non Finnish (NFE)

AF:

0.0487

AC:

51456

AN:

1056950

Other (OTH)

AF:

0.0683

AC:

3827

AN:

56024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

3275

6550

9824

13099

16374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1978

3956

5934

7912

9890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.130

AC:

19653

AN:

150620

Hom.:

2537

Cov.:

AF XY:

0.128

AC XY:

9424

AN XY:

73658

show subpopulations

African (AFR)

AF:

0.334

AC:

13468

AN:

40348

American (AMR)

AF:

0.0589

AC:

897

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.0829

AC:

287

AN:

3460

East Asian (EAS)

AF:

0.000969

AC:

AN:

5162

South Asian (SAS)

AF:

0.0654

AC:

312

AN:

4768

European-Finnish (FIN)

AF:

0.0560

AC:

589

AN:

10520

Middle Eastern (MID)

AF:

0.0856

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0568

AC:

3855

AN:

67826

Other (OTH)

AF:

0.0972

AC:

205

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

652

1304

1957

2609

3261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.115

Hom.:

249

Bravo

AF:

0.142

Asia WGS

AF:

0.0540

AC:

188

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.52

(source)

DANN

Benign

0.62

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over