Genetic Variant ELOVL4:c.*609G>A (chr6-79915999-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_022726.4(ELOVL4):c.*609G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 152,968 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.032 ( 109 hom., cov: 33)

Exomes 𝑓: 0.036 ( 0 hom. )

Consequence

ELOVL4
NM_022726.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.238

Variant links:

Genes affected

ELOVL4 (HGNC:14415): (ELOVL fatty acid elongase 4) This gene encodes a membrane-bound protein which is a member of the ELO family, proteins which participate in the biosynthesis of fatty acids. Consistent with the expression of the encoded protein in photoreceptor cells of the retina, mutations and small deletions in this gene are associated with Stargardt-like macular dystrophy (STGD3) and autosomal dominant Stargardt-like macular dystrophy (ADMD), also referred to as autosomal dominant atrophic macular degeneration. [provided by RefSeq, Jul 2008]

ELOVL4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

BP6

Variant 6-79915999-C-T is Benign according to our data. Variant chr6-79915999-C-T is described in ClinVar as [Benign]. Clinvar id is 358133.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELOVL4	NM_022726.4 link	c.*609G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000369816.5	NP_073563.1	Q9GZR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELOVL4	ENST00000369816 link	c.*609G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_022726.4	ENSP00000358831.4		Q9GZR5

Frequencies

GnomAD3 genomes

AF:

0.0320

AC:

4864

AN:

152128

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0532

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0248

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0497

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0225

Gnomad OTH

AF:

0.0301

GnomAD4 exome

AF:

0.0360

AC:

AN:

722

Hom.:

Cov.:

AF XY:

0.0287

AC XY:

AN XY:

418

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0556

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0491

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0320

AC:

4871

AN:

152246

Hom.:

109

Cov.:

AF XY:

0.0331

AC XY:

2462

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0533

Gnomad4 AMR

AF:

0.0247

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0497

Gnomad4 NFE

AF:

0.0225

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0294

Hom.:

Bravo

AF:

0.0304

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Stargardt disease 3

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.6

DANN

Benign

0.87

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