Genetic Variant ELAVL1:c.431-6G>A (chr19-7967796-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001419.3(ELAVL1):c.431-6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,606,192 control chromosomes in the GnomAD database, including 60,035 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6150 hom., cov: 33)

Exomes 𝑓: 0.27 ( 53885 hom. )

Consequence

ELAVL1
NM_001419.3 splice_region, intron

Scores

Splicing: ADA: 0.0001073

Clinical Significance

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

Conservation

PhyloP100: 0.109

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 19-7967796-C-T is Benign according to our data. Variant chr19-7967796-C-T is described in ClinVar as [Benign]. Clinvar id is 1182559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ELAVL1	NM_001419.3 link	c.431-6G>A	splice_region_variant, intron_variant	Intron 4 of 5	ENST00000407627.7	NP_001410.2	Q15717-1
ELAVL1	XM_047438383.1 link	c.512-6G>A	splice_region_variant, intron_variant	Intron 4 of 5		XP_047294339.1
ELAVL1	XM_047438384.1 link	c.512-3989G>A	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.431-6G>A	splice_region_variant, intron_variant	Intron 4 of 5	1	NM_001419.3	ENSP00000385269.1	Q15717-1
ELAVL1	ENST00000596459.5 link	c.431-6G>A	splice_region_variant, intron_variant	Intron 4 of 5	2		ENSP00000472197.1	Q15717-1
ELAVL1	ENST00000593807.1 link	c.*36-3989G>A	intron_variant	Intron 5 of 5	3		ENSP00000470727.1	M0QZR9
ELAVL1	ENST00000596154.5 link	c.184+5929G>A	intron_variant	Intron 2 of 2	3		ENSP00000471011.1	M0R055

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42013

AN:

151932

Hom.:

6140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.0742

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.229

AC:

56464

AN:

247060

Hom.:

7461

AF XY:

0.228

AC XY:

30460

AN XY:

133678

show subpopulations

Gnomad AFR exome

AF:

0.344

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.283

Gnomad EAS exome

AF:

0.0692

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.253

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.265

AC:

385465

AN:

1454142

Hom.:

53885

Cov.:

AF XY:

0.261

AC XY:

188811

AN XY:

722378

show subpopulations

Gnomad4 AFR exome

AF:

0.344

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.0683

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.260

GnomAD4 genome

AF:

0.277

AC:

42055

AN:

152050

Hom.:

6150

Cov.:

AF XY:

0.271

AC XY:

20144

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.338

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.287

Gnomad4 EAS

AF:

0.0742

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.239

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.275

Alfa

AF:

0.281

Hom.:

8159

Bravo

AF:

0.277

Asia WGS

AF:

0.118

AC:

409

AN:

3478

EpiCase

AF:

0.286

EpiControl

AF:

0.287

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.7

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0040

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

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