Genetic Variant ELAVL1:c.656+17C>T (chr19-7967548-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001419.3(ELAVL1):c.656+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,610,604 control chromosomes in the GnomAD database, including 52,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3916 hom., cov: 33)

Exomes 𝑓: 0.25 ( 48379 hom. )

Consequence

ELAVL1
NM_001419.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.495

Variant links:

Genes affected

ELAVL1 (HGNC:3312): (ELAV like RNA binding protein 1) The protein encoded by this gene is a member of the ELAVL family of RNA-binding proteins that contain several RNA recognition motifs, and selectively bind AU-rich elements (AREs) found in the 3' untranslated regions of mRNAs. AREs signal degradation of mRNAs as a means to regulate gene expression, thus by binding AREs, the ELAVL family of proteins play a role in stabilizing ARE-containing mRNAs. This gene has been implicated in a variety of biological processes and has been linked to a number of diseases, including cancer. It is highly expressed in many cancers, and could be potentially useful in cancer diagnosis, prognosis, and therapy. [provided by RefSeq, Sep 2012]

ELAVL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-7967548-G-A is Benign according to our data. Variant chr19-7967548-G-A is described in ClinVar as [Benign]. Clinvar id is 1237796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ELAVL1	NM_001419.3 link	c.656+17C>T	intron_variant	Intron 5 of 5	ENST00000407627.7	NP_001410.2	Q15717-1
ELAVL1	XM_047438383.1 link	c.737+17C>T	intron_variant	Intron 5 of 5		XP_047294339.1
ELAVL1	XM_047438384.1 link	c.512-3741C>T	intron_variant	Intron 4 of 4		XP_047294340.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ELAVL1	ENST00000407627.7 link	c.656+17C>T	intron_variant	Intron 5 of 5	1	NM_001419.3	ENSP00000385269.1	Q15717-1
ELAVL1	ENST00000596459.5 link	c.656+17C>T	intron_variant	Intron 5 of 5	2		ENSP00000472197.1	Q15717-1
ELAVL1	ENST00000593807.1 link	c.*36-3741C>T	intron_variant	Intron 5 of 5	3		ENSP00000470727.1	M0QZR9
ELAVL1	ENST00000596154.5 link	c.185-5936C>T	intron_variant	Intron 2 of 2	3		ENSP00000471011.1	M0R055

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30587

AN:

152056

Hom.:

3915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0465

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.204

GnomAD3 exomes

AF:

0.262

AC:

64454

AN:

246424

Hom.:

9379

AF XY:

0.261

AC XY:

34895

AN XY:

133610

show subpopulations

Gnomad AFR exome

AF:

0.0404

Gnomad AMR exome

AF:

0.312

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.495

Gnomad SAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.275

Gnomad NFE exome

AF:

0.247

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.250

AC:

364888

AN:

1458430

Hom.:

48379

Cov.:

AF XY:

0.250

AC XY:

181215

AN XY:

725312

show subpopulations

Gnomad4 AFR exome

AF:

0.0376

Gnomad4 AMR exome

AF:

0.305

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.508

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.246

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.201

AC:

30588

AN:

152174

Hom.:

3916

Cov.:

AF XY:

0.203

AC XY:

15137

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0463

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.283

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.222

Hom.:

948

Bravo

AF:

0.198

Asia WGS

AF:

0.301

AC:

1044

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 26, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.9

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over