rs12195587

Positions:

• chr6-10989709-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017770.4(ELOVL2):​c.759C>T​(p.Tyr253=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,611,924 control chromosomes in the GnomAD database, including 20,554 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 0.11 (1224 hom., cov: 33)
  • Exomes 𝑓: 0.15 (19330 hom.)
• Consequence: ELOVL2 NM_017770.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136

Genes affected

ELOVL2 (HGNC:14416): (ELOVL fatty acid elongase 2) Enables fatty acid elongase activity. Involved in fatty acid elongation, polyunsaturated fatty acid and very long-chain fatty acid biosynthetic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=0.136 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELOVL2	NM_017770.4	c.759C>T	p.Tyr253=	synonymous_variant	7/8	ENST00000354666.4	NP_060240.3
ELOVL2	XM_011514716.4	c.849C>T	p.Tyr283=	synonymous_variant	7/8		XP_011513018.1
ELOVL2	XM_011514717.4	c.762C>T	p.Tyr254=	synonymous_variant	7/8		XP_011513019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELOVL2	ENST00000354666.4	c.759C>T	p.Tyr253=	synonymous_variant	7/8	1	NM_017770.4	ENSP00000346693	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16644 AN: 151918 Hom.: 1225 Cov.: 33

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.0951

GnomAD3 exomes AF: 0.117 AC: 29344 AN: 251236 Hom.: 2226 AF XY: 0.120 AC XY: 16360 AN XY: 135770

Gnomad AFR exome AF: 0.0284

Gnomad AMR exome AF: 0.0648

Gnomad ASJ exome AF: 0.0819

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.0951

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.155 AC: 225639 AN: 1459900 Hom.: 19330 Cov.: 33 AF XY: 0.153 AC XY: 111255 AN XY: 726334

Gnomad4 AFR exome AF: 0.0247

Gnomad4 AMR exome AF: 0.0671

Gnomad4 ASJ exome AF: 0.0771

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.0984

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.109 AC: 16638 AN: 152024 Hom.: 1224 Cov.: 33 AF XY: 0.107 AC XY: 7921 AN XY: 74310

Gnomad4 AFR AF: 0.0321

Gnomad4 AMR AF: 0.0802

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0827

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.0937

Alfa AF: 0.149 Hom.: 2392

Bravo AF: 0.102

Asia WGS AF: 0.0320 AC: 112 AN: 3478

EpiCase AF: 0.155

EpiControl AF: 0.152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs12195587; hg19: chr6-10989942; COSMIC: COSV61155243;