rs17415911

Positions:

• chr15-50205097-A-G
• chr15-50205097-A-T

Variant summary

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

The NM_003645.4(SLC27A2):​c.848-142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 904,052 control chromosomes in the GnomAD database, including 11,316 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 0.12 (1387 hom., cov: 30)
  • Exomes 𝑓: 0.15 (9929 hom.)
• Consequence: SLC27A2 NM_003645.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC27A2	NM_003645.4	c.848-142A>G		intron_variant		ENST00000267842.10	NP_003636.2
SLC27A2	NM_001159629.2	c.689-142A>G		intron_variant			NP_001153101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC27A2	ENST00000267842.10	c.848-142A>G		intron_variant		1	NM_003645.4	ENSP00000267842.5
SLC27A2	ENST00000380902.8	c.689-142A>G		intron_variant		1		ENSP00000370289.4
SLC27A2	ENST00000544960.1	c.143-142A>G		intron_variant		2		ENSP00000444549.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18416 AN: 151852 Hom.: 1387 Cov.: 30

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.155 AC: 116201 AN: 752086 Hom.: 9929 AF XY: 0.154 AC XY: 57921 AN XY: 375584

Gnomad4 AFR exome AF: 0.0501

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.000615

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.0817

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.121 AC: 18415 AN: 151966 Hom.: 1387 Cov.: 30 AF XY: 0.117 AC XY: 8721 AN XY: 74282

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0665

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.146

Alfa AF: 0.130 Hom.: 207

Bravo AF: 0.123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17415911; hg19: chr15-50497294;