NM_003645.4:c.479-3310C>T

Variant names:

• chr15-50194190-C-T
• rs1797316
• NM_003645.4:c.479-3310C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003645.4. 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
	SLC27A2	NM_003645.4	MANE Select	c.479-3310C>T		intron	N/A	NP_003636.2	O14975-1
	SLC27A2	NM_001159629.2		c.479-3310C>T		intron	N/A	NP_001153101.1	O14975-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC27A2	ENST00000267842.10	TSL:1 MANE Select	c.479-3310C>T		intron	N/A	ENSP00000267842.5	O14975-1
	SLC27A2	ENST00000380902.8	TSL:1	c.479-3310C>T		intron	N/A	ENSP00000370289.4	O14975-2
	SLC27A2	ENST00000895509.1		c.479-3310C>T		intron	N/A	ENSP00000565568.1

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

African (AFR) AF: 0.713 AC: 29540 AN: 41414

American (AMR) AF: 0.853 AC: 13036 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3154 AN: 3472

East Asian (EAS) AF: 0.952 AC: 4925 AN: 5172

South Asian (SAS) AF: 0.878 AC: 4222 AN: 4810

European-Finnish (FIN) AF: 0.966 AC: 10245 AN: 10608

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61997 AN: 68022

Other (OTH) AF: 0.859 AC: 1815 AN: 2112

Alfa AF: 0.890 Hom.: 9203

Bravo AF: 0.841

Asia WGS AF: 0.901 AC: 3134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.29
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1797316; hg19: chr15-50486387;