6-53269450-C-CT

Variant names:

• chr6-53269450-C-CT
• rs3215545
• NM_021814.5:c.757-181dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_021814.5(ELOVL5):​c.757-181dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 147,294 control chromosomes in the GnomAD database, including 39 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.014 (39 hom., cov: 32)
• Consequence: ELOVL5 NM_021814.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.381
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 6-53269450-C-CT is Benign according to our data. Variant chr6-53269450-C-CT is described in ClinVar as Likely_benign. ClinVar VariationId is 1321663.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0142 (2091/147294) while in subpopulation AFR AF = 0.0403 (1629/40464). AF 95% confidence interval is 0.0386. There are 39 homozygotes in GnomAd4. There are 995 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2091 AD gene.

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.757-181dupA		intron	N/A	NP_068586.1	Q9NYP7-1
	ELOVL5	NM_001242828.2		c.838-181dupA		intron	N/A	NP_001229757.1	Q9NYP7-2
	ELOVL5	NM_001301856.2		c.757-181dupA		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.757-181_757-180insA		intron	N/A	ENSP00000306640.6	Q9NYP7-1
	ELOVL5	ENST00000542638.5	TSL:1	c.632-181_632-180insA		intron	N/A	ENSP00000440728.2	A0A0A0MTI6
	ELOVL5	ENST00000370918.8	TSL:2	c.838-181_838-180insA		intron	N/A	ENSP00000359956.5	Q9NYP7-2

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2084 AN: 147240 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00626

Gnomad ASJ AF: 0.000588

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00277

Gnomad FIN AF: 0.00137

Gnomad MID AF: 0.0229

Gnomad NFE AF: 0.00469

Gnomad OTH AF: 0.0121

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

GnomAD4 genome AF: 0.0142 AC: 2091 AN: 147294 Hom.: 39 Cov.: 32 AF XY: 0.0139 AC XY: 995 AN XY: 71762

African (AFR) AF: 0.0403 AC: 1629 AN: 40464

American (AMR) AF: 0.00625 AC: 92 AN: 14710

Ashkenazi Jewish (ASJ) AF: 0.000588 AC: 2 AN: 3404

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5066

South Asian (SAS) AF: 0.00278 AC: 13 AN: 4670

European-Finnish (FIN) AF: 0.00137 AC: 13 AN: 9464

Middle Eastern (MID) AF: 0.0213 AC: 6 AN: 282

European-Non Finnish (NFE) AF: 0.00469 AC: 311 AN: 66322

Other (OTH) AF: 0.0120 AC: 24 AN: 2002

Alfa AF: 0.000550 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely 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
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

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: rs3215545; hg19: chr6-53134248; COSMIC: COSV58650292;