rs148919174

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022726.4(ELOVL4):c.814G>C(p.Glu272Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,614,028 control chromosomes in the GnomAD database, including 150 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 19 hom., cov: 33)

Exomes 𝑓: 0.011 ( 131 hom. )

Consequence

ELOVL4
NM_022726.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.191

Publications

14 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):

ELOVL4-related maculopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Stargardt disease 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
spinocerebellar ataxia type 34
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, 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=0.0019508898).

BP6

Variant 6-79916739-C-G is Benign according to our data. Variant chr6-79916739-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00894 (1360/152164) while in subpopulation NFE AF = 0.0135 (915/68018). AF 95% confidence interval is 0.0127. There are 19 homozygotes in GnomAd4. There are 693 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022726.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELOVL4	NM_022726.4	MANE Select	c.814G>C	p.Glu272Gln	missense	Exon 6 of 6	NP_073563.1	Q9GZR5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELOVL4	ENST00000369816.5	TSL:1 MANE Select	c.814G>C	p.Glu272Gln	missense	Exon 6 of 6	ENSP00000358831.4	Q9GZR5

Frequencies

GnomAD3 genomes

AF:

0.00894

AC:

1360

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00943

AC:

2370

AN:

251324

AF XY:

0.00922

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0287

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0108

AC:

15784

AN:

1461864

Hom.:

131

Cov.:

AF XY:

0.0106

AC XY:

7742

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

33480

American (AMR)

AF:

0.00277

AC:

124

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00360

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00285

AC:

246

AN:

86258

European-Finnish (FIN)

AF:

0.0292

AC:

1562

AN:

53416

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0119

AC:

13205

AN:

1112002

Other (OTH)

AF:

0.00801

AC:

484

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

963

1926

2889

3852

4815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.00894

AC:

1360

AN:

152164

Hom.:

Cov.:

AF XY:

0.00932

AC XY:

693

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00198

AC:

AN:

41512

American (AMR)

AF:

0.00275

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00374

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0273

AC:

289

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0135

AC:

915

AN:

68018

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

148

221

295

369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0111

Hom.:

Bravo

AF:

0.00665

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0134

AC:

115

ExAC

AF:

0.00982

AC:

1192

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00998

EpiControl

AF:

0.00871

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (1)

Stargardt disease 3 (1)

Stargardt disease 3;C1851481:Spinocerebellar ataxia type 34;C3280856:Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.035

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.75

PhyloP100

0.19

PrimateAI

Benign

0.32

PROVEAN

Benign

0.31

REVEL

Benign

0.016

Sift

Benign

0.57

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.062

MVP

0.068

MPC

0.37

ClinPred

0.00077

GERP RS

3.1

Varity_R

0.14

gMVP

0.53

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over