6-53278756-T-C

Variant names:

• chr6-53278756-T-C
• rs2281274
• NM_021814.5:c.247-2500A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021814.5(ELOVL5):​c.247-2500A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,994 control chromosomes in the GnomAD database, including 7,423 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7423 hom., cov: 32)
• Consequence: ELOVL5 NM_021814.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 4 publications found

Genes affected

ELOVL5 (HGNC:21308): (ELOVL fatty acid elongase 5) This gene belongs to the ELO family. It is highly expressed in the adrenal gland and testis, and encodes a multi-pass membrane protein that is localized in the endoplasmic reticulum. This protein is involved in the elongation of long-chain polyunsaturated fatty acids. Mutations in this gene have been associated with spinocerebellar ataxia-38 (SCA38). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

ELOVL5 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 38

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021814.5. 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
	ELOVL5	NM_021814.5	MANE Select	c.247-2500A>G		intron	N/A	NP_068586.1	Q9NYP7-1
	ELOVL5	NM_001242828.2		c.328-2500A>G		intron	N/A	NP_001229757.1	Q9NYP7-2
	ELOVL5	NM_001301856.2		c.247-2500A>G		intron	N/A	NP_001288785.1	Q9NYP7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELOVL5	ENST00000304434.11	TSL:1 MANE Select	c.247-2500A>G		intron	N/A	ENSP00000306640.6	Q9NYP7-1
	ELOVL5	ENST00000542638.5	TSL:1	c.247-2500A>G		intron	N/A	ENSP00000440728.2	A0A0A0MTI6
	ELOVL5	ENST00000370918.8	TSL:2	c.328-2500A>G		intron	N/A	ENSP00000359956.5	Q9NYP7-2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43466 AN: 151876 Hom.: 7406 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.286 AC: 43517 AN: 151994 Hom.: 7423 Cov.: 32 AF XY: 0.286 AC XY: 21222 AN XY: 74298

African (AFR) AF: 0.487 AC: 20147 AN: 41392

American (AMR) AF: 0.205 AC: 3140 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 906 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1016 AN: 5152

South Asian (SAS) AF: 0.223 AC: 1078 AN: 4824

European-Finnish (FIN) AF: 0.192 AC: 2032 AN: 10586

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14262 AN: 67976

Other (OTH) AF: 0.302 AC: 637 AN: 2108

Alfa AF: 0.230 Hom.: 9453

Bravo AF: 0.298

Asia WGS AF: 0.198 AC: 687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.85
PhyloP100		-1.1
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: rs2281274; hg19: chr6-53143554;