rs3812153

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

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

Publications

47 publications found

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 Gene-Disease associations (from GenCC):

Stargardt disease 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia
spinocerebellar ataxia type 34
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet
Stargardt disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ELOVL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 137206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

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

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

GnomAD2 exomes

AF:

0.167

AC:

41850

AN:

251258

AF XY:

0.173

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 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

African (AFR)

AF:

0.236

AC:

7895

AN:

33474

American (AMR)

AF:

0.176

AC:

7846

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0975

AC:

2547

AN:

26134

East Asian (EAS)

AF:

0.204

AC:

8103

AN:

39694

South Asian (SAS)

AF:

0.350

AC:

30172

AN:

86250

European-Finnish (FIN)

AF:

0.117

AC:

6223

AN:

53412

Middle Eastern (MID)

AF:

0.130

AC:

752

AN:

5766

European-Non Finnish (NFE)

AF:

0.112

AC:

124820

AN:

1111880

Other (OTH)

AF:

0.146

AC:

8812

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

9439

18878

28316

37755

47194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4850

9700

14550

19400

24250

<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:

0.160

AC:

24411

AN:

152228

Hom.:

2242

Cov.:

AF XY:

0.163

AC XY:

12153

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.230

AC:

9570

AN:

41520

American (AMR)

AF:

0.162

AC:

2476

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

352

AN:

3468

East Asian (EAS)

AF:

0.200

AC:

1038

AN:

5182

South Asian (SAS)

AF:

0.357

AC:

1721

AN:

4826

European-Finnish (FIN)

AF:

0.114

AC:

1210

AN:

10604

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7569

AN:

68014

Other (OTH)

AF:

0.133

AC:

281

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1022

2044

3067

4089

5111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<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:

0.127

Hom.:

6294

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

Dec 17, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Stargardt disease 3

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

(source)

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

PhyloP100

1.9

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

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over