rs1802536

chr15-50236217-C-Achr15-50236217-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003645.4(SLC27A2):c.*121C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 743,338 control chromosomes in the GnomAD database, including 8,246 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 0.16 (2019 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6227 hom.)
• Consequence: SLC27A2 NM_003645.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

Genes affected

SLC27A2 (HGNC:10996): (solute carrier family 27 member 2) The protein encoded by this gene is an isozyme of long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. This isozyme activates long-chain, branched-chain and very-long-chain fatty acids containing 22 or more carbons to their CoA derivatives. It is expressed primarily in liver and kidney, and is present in both endoplasmic reticulum and peroxisomes, but not in mitochondria. Its decreased peroxisomal enzyme activity is in part responsible for the biochemical pathology in X-linked adrenoleukodystrophy. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC27A2	NM_003645.4	c.*121C>A		3_prime_UTR_variant	10/10	ENST00000267842.10
SLC27A2	NM_001159629.2	c.*121C>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC27A2	ENST00000267842.10	c.*121C>A		3_prime_UTR_variant	10/10	1	NM_003645.4	P1
SLC27A2	ENST00000380902.8	c.*121C>A		3_prime_UTR_variant	9/9	1
SLC27A2	ENST00000544960.1	c.*121C>A		3_prime_UTR_variant	11/11	2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24135 AN: 151962 Hom.: 2019 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.140 AC: 82596 AN: 591258 Hom.: 6227 Cov.: 8 AF XY: 0.139 AC XY: 41930 AN XY: 302142

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.0178

Gnomad4 SAS exome AF: 0.0885

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.159 AC: 24151 AN: 152080 Hom.: 2019 Cov.: 32 AF XY: 0.157 AC XY: 11644 AN XY: 74326

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0320

Gnomad4 SAS AF: 0.0717

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.144

Alfa AF: 0.111 Hom.: 272

Bravo AF: 0.161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.26
Dann	Benign	0.34

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: rs1802536; hg19: chr15-50528414;