6-79915542-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022726.4(ELOVL4):c.*1066T>G 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 152,632 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (108 hom., cov: 33)
  • Exomes 𝑓: 0.051 (0 hom.)
• Consequence: ELOVL4 NM_022726.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.05

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 6-79915542-A-C is Benign according to our data. Variant chr6-79915542-A-C is described in ClinVar as [Benign]. Clinvar id is 358126.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELOVL4	NM_022726.4	c.*1066T>G		3_prime_UTR_variant	6/6	ENST00000369816.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELOVL4	ENST00000369816.5	c.*1066T>G		3_prime_UTR_variant	6/6	1	NM_022726.4	P1

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4863 AN: 152178 Hom.: 107 Cov.: 33

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0301

GnomAD4 exome AF: 0.0506 AC: 17 AN: 336 Hom.: 0 Cov.: 0 AF XY: 0.0437 AC XY: 9 AN XY: 206

Gnomad4 FIN exome AF: 0.0509

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0320 AC: 4870 AN: 152296 Hom.: 108 Cov.: 33 AF XY: 0.0331 AC XY: 2464 AN XY: 74470

Gnomad4 AFR AF: 0.0531

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0496

Gnomad4 NFE AF: 0.0225

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0293 Hom.: 22

Bravo AF: 0.0304

Asia WGS AF: 0.00927 AC: 32 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Stargardt disease 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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	-0.54
Cadd	Benign	11
Dann	Benign	0.84

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

Other links and lift over

dbSNP: rs45594338; hg19: chr6-80625259;