6-53269050-T-C

Position:

• chr6-53269050-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_021814.5(ELOVL5):​c.*77A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,534,138 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0099 (13 hom., cov: 32)
  • Exomes 𝑓: 0.013 (159 hom.)
• Consequence: ELOVL5 NM_021814.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.87

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-53269050-T-C is Benign according to our data. Variant chr6-53269050-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1343009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1506 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL5	NM_021814.5	c.*77A>G		3_prime_UTR_variant	8/8	ENST00000304434.11	NP_068586.1
ELOVL5	NM_001242828.2	c.*77A>G		3_prime_UTR_variant	9/9		NP_001229757.1
ELOVL5	NM_001301856.2	c.*77A>G		3_prime_UTR_variant	8/8		NP_001288785.1
ELOVL5	NM_001242830.2	c.*63A>G		3_prime_UTR_variant	7/7		NP_001229759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELOVL5	ENST00000304434	c.*77A>G		3_prime_UTR_variant	8/8	1	NM_021814.5	ENSP00000306640.6
ELOVL5	ENST00000542638	c.*63A>G		3_prime_UTR_variant	7/7	1		ENSP00000440728.2
ELOVL5	ENST00000370918	c.*77A>G		3_prime_UTR_variant	9/9	2		ENSP00000359956.5

Frequencies

GnomAD3 genomes AF: 0.00988 AC: 1504 AN: 152200 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00246

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0157

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.0129 AC: 17883 AN: 1381820 Hom.: 159 Cov.: 21 AF XY: 0.0128 AC XY: 8759 AN XY: 683610

Gnomad4 AFR exome AF: 0.00201

Gnomad4 AMR exome AF: 0.00535

Gnomad4 ASJ exome AF: 0.00848

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00224

Gnomad4 FIN exome AF: 0.0214

Gnomad4 NFE exome AF: 0.0146

Gnomad4 OTH exome AF: 0.00997

GnomAD4 genome AF: 0.00989 AC: 1506 AN: 152318 Hom.: 13 Cov.: 32 AF XY: 0.00996 AC XY: 742 AN XY: 74494

Gnomad4 AFR AF: 0.00245

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0157

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.0111 Hom.: 0

Bravo AF: 0.00881

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 23, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41273876; hg19: chr6-53133848;