6-79915812-CAT-C

Variant names:

• chr6-79915812-CAT-C
• rs140197858
• NM_022726.4:c.*794_*795delAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_022726.4(ELOVL4):​c.*794_*795delAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,490 control chromosomes in the GnomAD database, including 1,902 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1900 hom., cov: 30)
  • Exomes 𝑓: 0.12 (2 hom.)
• Consequence: ELOVL4 NM_022726.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.57
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-79915812-CAT-C is Benign according to our data. Variant chr6-79915812-CAT-C is described in ClinVar as Benign. ClinVar VariationId is 358131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

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.*794_*795delAT		3_prime_UTR	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.*794_*795delAT		3_prime_UTR	Exon 6 of 6	ENSP00000358831.4	Q9GZR5

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22687 AN: 151938 Hom.: 1902 Cov.: 30

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.118 AC: 51 AN: 434 Hom.: 2 AF XY: 0.134 AC XY: 35 AN XY: 262

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.117 AC: 50 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.149 AC: 22690 AN: 152056 Hom.: 1900 Cov.: 30 AF XY: 0.153 AC XY: 11352 AN XY: 74350

African (AFR) AF: 0.194 AC: 8046 AN: 41470

American (AMR) AF: 0.156 AC: 2391 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3470

East Asian (EAS) AF: 0.200 AC: 1032 AN: 5166

South Asian (SAS) AF: 0.356 AC: 1718 AN: 4820

European-Finnish (FIN) AF: 0.114 AC: 1204 AN: 10566

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.110 AC: 7491 AN: 67968

Other (OTH) AF: 0.128 AC: 270 AN: 2110

Alfa AF: 0.125 Hom.: 152

Bravo AF: 0.150

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Stargardt Disease, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs140197858; hg19: chr6-80625529;