NM_003645.4:c.1556-1195T>C

Variant names:

• chr15-50232673-T-C
• rs10519263
• NM_003645.4:c.1556-1195T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003645.4(SLC27A2):​c.1556-1195T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,010 control chromosomes in the GnomAD database, including 1,701 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 0.15 (1701 hom., cov: 31)
• Consequence: SLC27A2 NM_003645.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC27A2	NM_003645.4	c.1556-1195T>C		intron_variant	Intron 8 of 9	ENST00000267842.10	NP_003636.2
SLC27A2	NM_001159629.2	c.1397-1195T>C		intron_variant	Intron 7 of 8		NP_001153101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC27A2	ENST00000267842.10	c.1556-1195T>C		intron_variant	Intron 8 of 9	1	NM_003645.4	ENSP00000267842.5
SLC27A2	ENST00000380902.8	c.1397-1195T>C		intron_variant	Intron 7 of 8	1		ENSP00000370289.4
SLC27A2	ENST00000544960.1	c.851-1195T>C		intron_variant	Intron 9 of 10	2		ENSP00000444549.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22310 AN: 151892 Hom.: 1700 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.147 AC: 22322 AN: 152010 Hom.: 1701 Cov.: 31 AF XY: 0.147 AC XY: 10914 AN XY: 74318

African (AFR) AF: 0.149 AC: 6189 AN: 41446

American (AMR) AF: 0.137 AC: 2095 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3468

East Asian (EAS) AF: 0.0324 AC: 167 AN: 5156

South Asian (SAS) AF: 0.0715 AC: 344 AN: 4808

European-Finnish (FIN) AF: 0.186 AC: 1970 AN: 10564

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10535 AN: 67980

Other (OTH) AF: 0.144 AC: 305 AN: 2112

Alfa AF: 0.149 Hom.: 1070

Bravo AF: 0.143

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.20
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10519263; hg19: chr15-50524870;