rs2294859

Variant names:

• chr6-53294778-T-C
• rs2294859
• NM_021814.5:c.58+864A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021814.5(ELOVL5):​c.58+864A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0623 in 152,248 control chromosomes in the GnomAD database, including 597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.062 (597 hom., cov: 32)
• Consequence: ELOVL5 NM_021814.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.452
• Publications: 2 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), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-53294778-T-C is Benign according to our data. Variant chr6-53294778-T-C is described in ClinVar as Benign. ClinVar VariationId is 1248645.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 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.58+864A>G		intron	N/A	NP_068586.1	Q9NYP7-1
	ELOVL5	NM_001242828.2		c.58+864A>G		intron	N/A	NP_001229757.1	Q9NYP7-2
	ELOVL5	NM_001301856.2		c.58+864A>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.58+864A>G		intron	N/A	ENSP00000306640.6	Q9NYP7-1
	ELOVL5	ENST00000542638.5	TSL:1	c.58+864A>G		intron	N/A	ENSP00000440728.2	A0A0A0MTI6
	ELOVL5	ENST00000370913.5	TSL:1	c.59-287A>G		intron	N/A	ENSP00000359951.5	Q9NYP7-3

Frequencies

GnomAD3 genomes AF: 0.0623 AC: 9479 AN: 152130 Hom.: 590 Cov.: 32

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.0456

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0906

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

GnomAD4 genome AF: 0.0623 AC: 9491 AN: 152248 Hom.: 597 Cov.: 32 AF XY: 0.0628 AC XY: 4673 AN XY: 74448

African (AFR) AF: 0.0156 AC: 650 AN: 41540

American (AMR) AF: 0.216 AC: 3298 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 223 AN: 3470

East Asian (EAS) AF: 0.0457 AC: 237 AN: 5190

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4822

European-Finnish (FIN) AF: 0.0195 AC: 207 AN: 10612

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0633 AC: 4303 AN: 68006

Other (OTH) AF: 0.0892 AC: 188 AN: 2108

Alfa AF: 0.0858 Hom.: 174

Bravo AF: 0.0802

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.71
PhyloP100		0.45
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: rs2294859; hg19: chr6-53159576;