6-53269277-T-C

Variant names:

• chr6-53269277-T-C
• rs948474141
• NM_021814.5:c.757-7A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_021814.5(ELOVL5):​c.757-7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,602,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ELOVL5 NM_021814.5 splice_region, intron
• Scores: Splicing: ADA: 0.00002693
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72
• 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-53269277-T-C is Benign according to our data. Variant chr6-53269277-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3685703.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 8 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.757-7A>G		splice_region intron	N/A	NP_068586.1	Q9NYP7-1
	ELOVL5	NM_001242828.2		c.838-7A>G		splice_region intron	N/A	NP_001229757.1	Q9NYP7-2
	ELOVL5	NM_001301856.2		c.757-7A>G		splice_region 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.757-7A>G		splice_region intron	N/A	ENSP00000306640.6	Q9NYP7-1
	ELOVL5	ENST00000542638.5	TSL:1	c.632-7A>G		splice_region intron	N/A	ENSP00000440728.2	A0A0A0MTI6
	ELOVL5	ENST00000370918.8	TSL:2	c.838-7A>G		splice_region intron	N/A	ENSP00000359956.5	Q9NYP7-2

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 148386 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000168 AC: 4 AN: 238606 AF XY: 0.0000309

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000277

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.00000550 AC: 8 AN: 1454348 Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 4 AN XY: 723336

African (AFR) AF: 0.00 AC: 0 AN: 32952

American (AMR) AF: 0.0000231 AC: 1 AN: 43258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25858

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 85026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000631 AC: 7 AN: 1108576

Other (OTH) AF: 0.00 AC: 0 AN: 60068

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 148386 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72380

African (AFR) AF: 0.00 AC: 0 AN: 38854

American (AMR) AF: 0.00 AC: 0 AN: 14888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67654

Other (OTH) AF: 0.00 AC: 0 AN: 2016

Alfa AF: 0.0000712 Hom.: 0

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.50
PhyloP100		-1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.038
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: rs948474141; hg19: chr6-53134075;