chr6-53283221-T-C

Variant names:

• chr6-53283221-T-C
• rs17544464
• NM_021814.5:c.247-6965A>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.247-6965A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0622 in 152,292 control chromosomes in the GnomAD database, including 593 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 0.062 (593 hom., cov: 32)
• Consequence: ELOVL5 NM_021814.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELOVL5	NM_021814.5	MANE Select	c.247-6965A>G		intron	N/A	NP_068586.1
	ELOVL5	NM_001242828.2		c.327+4641A>G		intron	N/A	NP_001229757.1
	ELOVL5	NM_001301856.2		c.247-6965A>G		intron	N/A	NP_001288785.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELOVL5	ENST00000304434.11	TSL:1 MANE Select	c.247-6965A>G		intron	N/A	ENSP00000306640.6
	ELOVL5	ENST00000542638.5	TSL:1	c.247-6965A>G		intron	N/A	ENSP00000440728.2
	ELOVL5	ENST00000370918.8	TSL:2	c.327+4641A>G		intron	N/A	ENSP00000359956.5

Frequencies

GnomAD3 genomes AF: 0.0622 AC: 9460 AN: 152174 Hom.: 586 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: 0.0444

Gnomad SAS AF: 0.0339

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0632

Gnomad OTH AF: 0.0896

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

GnomAD4 genome AF: 0.0622 AC: 9472 AN: 152292 Hom.: 593 Cov.: 32 AF XY: 0.0626 AC XY: 4666 AN XY: 74492

African (AFR) AF: 0.0156 AC: 650 AN: 41570

American (AMR) AF: 0.215 AC: 3290 AN: 15274

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

East Asian (EAS) AF: 0.0445 AC: 231 AN: 5188

South Asian (SAS) AF: 0.0344 AC: 166 AN: 4830

European-Finnish (FIN) AF: 0.0196 AC: 208 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0632 AC: 4300 AN: 68026

Other (OTH) AF: 0.0882 AC: 186 AN: 2108

Alfa AF: 0.0636 Hom.: 60

Bravo AF: 0.0801

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.47
DANN	Benign	0.44
PhyloP100		0.066
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: rs17544464; hg19: chr6-53148019;