rs3812153

Variant names:

Variant summary

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

The NM_022726.4(ELOVL4):c.895A>G(p.Met299Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,932 control chromosomes in the GnomAD database, including 18,505 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2242 hom., cov: 33)

Exomes 𝑓: 0.13 ( 16263 hom. )

Consequence

ELOVL4
NM_022726.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.91

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:

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 (MetaRNN=0.0042957664).

BP6

Variant 6-79916658-T-C is Benign according to our data. Variant chr6-79916658-T-C is described in ClinVar as [Benign]. Clinvar id is 137206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-79916658-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELOVL4	NM_022726.4 link	c.895A>G	p.Met299Val	missense_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	ENST00000369816.5 link	c.895A>G	p.Met299Val	missense_variant	Exon 6 of 6	1	NM_022726.4	ENSP00000358831.4		Q9GZR5

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24394

AN:

152110

Hom.:

2243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.167

AC:

41850

AN:

251258

Hom.:

4385

AF XY:

0.173

AC XY:

23482

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.0976

Gnomad EAS exome

AF:

0.206

Gnomad SAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.114

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.135

AC:

197170

AN:

1461704

Hom.:

16263

Cov.:

AF XY:

0.141

AC XY:

102534

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.236

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.0975

Gnomad4 EAS exome

AF:

0.204

Gnomad4 SAS exome

AF:

0.350

Gnomad4 FIN exome

AF:

0.117

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.160

AC:

24411

AN:

152228

Hom.:

2242

Cov.:

AF XY:

0.163

AC XY:

12153

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.357

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.123

Hom.:

3220

Bravo

AF:

0.163

TwinsUK

AF:

0.116

AC:

431

ALSPAC

AF:

0.116

AC:

448

ESP6500AA

AF:

0.229

AC:

1008

ESP6500EA

AF:

0.109

AC:

939

ExAC

AF:

0.171

AC:

20786

Asia WGS

AF:

0.276

AC:

961

AN:

3478

EpiCase

AF:

0.110

EpiControl

AF:

0.113

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jun 28, 2011

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Dec 17, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Stargardt disease 3

Benign:2

Mar 06, 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. -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spinocerebellar ataxia type 34

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.22

DEOGEN2

Benign

0.018

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.094

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.81

PrimateAI

Benign

0.37

PROVEAN

Benign

0.22

REVEL

Benign

0.076

Sift

Benign

1.0

Sift4G

Benign

0.81

Polyphen

0.0

Vest4

0.021

MPC

0.38

ClinPred

0.0020

GERP RS

5.6

Varity_R

0.11

gMVP

0.22

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