6-53269166-C-A

Position:

• chr6-53269166-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001242830.2(ELOVL5):​c.736G>T​(p.Gly246*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,613,836 control chromosomes in the GnomAD database, including 793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (52 hom., cov: 32)
  • Exomes 𝑓: 0.029 (741 hom.)
• Consequence: ELOVL5 NM_001242830.2 stop_gained
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.492

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 6-53269166-C-A is Benign according to our data. Variant chr6-53269166-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1316416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0189 (2884/152216) while in subpopulation NFE AF= 0.0305 (2074/68024). AF 95% confidence interval is 0.0294. There are 52 homozygotes in gnomad4. There are 1319 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2884 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL5	NM_021814.5	c.861G>T	p.Leu287Leu	synonymous_variant	8/8	ENST00000304434.11	NP_068586.1
ELOVL5	NM_001242830.2	c.736G>T	p.Gly246*	stop_gained	7/7		NP_001229759.1
ELOVL5	NM_001242828.2	c.942G>T	p.Leu314Leu	synonymous_variant	9/9		NP_001229757.1
ELOVL5	NM_001301856.2	c.861G>T	p.Leu287Leu	synonymous_variant	8/8		NP_001288785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELOVL5	ENST00000542638.5	c.736G>T	p.Gly246*	stop_gained	7/7	1		ENSP00000440728.2
ELOVL5	ENST00000304434.11	c.861G>T	p.Leu287Leu	synonymous_variant	8/8	1	NM_021814.5	ENSP00000306640.6
ELOVL5	ENST00000370918.8	c.942G>T	p.Leu314Leu	synonymous_variant	9/9	2		ENSP00000359956.5

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2882 AN: 152098 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00604

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00934

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0305

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.0189 AC: 4744 AN: 251012 Hom.: 69 AF XY: 0.0192 AC XY: 2599 AN XY: 135692

Gnomad AFR exome AF: 0.00492

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.00844

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00964

Gnomad FIN exome AF: 0.0191

Gnomad NFE exome AF: 0.0295

Gnomad OTH exome AF: 0.0219

GnomAD4 exome AF: 0.0288 AC: 42036 AN: 1461620 Hom.: 741 Cov.: 31 AF XY: 0.0280 AC XY: 20372 AN XY: 727106

Gnomad4 AFR exome AF: 0.00424

Gnomad4 AMR exome AF: 0.0121

Gnomad4 ASJ exome AF: 0.00842

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00997

Gnomad4 FIN exome AF: 0.0187

Gnomad4 NFE exome AF: 0.0339

Gnomad4 OTH exome AF: 0.0254

GnomAD4 genome AF: 0.0189 AC: 2884 AN: 152216 Hom.: 52 Cov.: 32 AF XY: 0.0177 AC XY: 1319 AN XY: 74420

Gnomad4 AFR AF: 0.00602

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00955

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.0305

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0259 Hom.: 38

Bravo AF: 0.0185

TwinsUK AF: 0.0302 AC: 112

ALSPAC AF: 0.0324 AC: 125

ESP6500AA AF: 0.00772 AC: 34

ESP6500EA AF: 0.0293 AC: 252

ExAC AF: 0.0193 AC: 2345

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0276

EpiControl AF: 0.0292

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 26, 2022	See Variant Classification Assertion Criteria. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.8
DANN	Benign	0.75
FATHMM_MKL	Uncertain	0.79	D
Vest4		0.30
GERP RS		4.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs41273878; hg19: chr6-53133964; COSMIC: COSV58653552;