15-50194190-C-T

Position:

• chr15-50194190-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.479-3310C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 152,102 control chromosomes in the GnomAD database, including 56,216 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 0.86 (56216 hom., cov: 30)
• Consequence: SLC27A2 NM_003645.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC27A2	NM_003645.4	c.479-3310C>T		intron_variant		ENST00000267842.10
SLC27A2	NM_001159629.2	c.479-3310C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC27A2	ENST00000267842.10	c.479-3310C>T		intron_variant		1	NM_003645.4	P1
SLC27A2	ENST00000380902.8	c.479-3310C>T		intron_variant		1
SLC27A2	ENST00000544960.1	c.-476+3086C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129969 AN: 151984 Hom.: 56190 Cov.: 30

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.858

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.855 AC: 130053 AN: 152102 Hom.: 56216 Cov.: 30 AF XY: 0.860 AC XY: 63944 AN XY: 74358

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.952

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.859

Alfa AF: 0.896 Hom.: 9004

Bravo AF: 0.841

Asia WGS AF: 0.901 AC: 3134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.29

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: rs1797316; hg19: chr15-50486387;