chr15-50205651-G-T

Variant names:

• chr15-50205651-G-T
• rs2278167
• NM_003645.4:c.972+288G>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.972+288G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,854 control chromosomes in the GnomAD database, including 17,388 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 0.46 (17388 hom., cov: 31)
• Consequence: SLC27A2 NM_003645.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC27A2	NM_003645.4	MANE Select	c.972+288G>T		intron	N/A	NP_003636.2
	SLC27A2	NM_001159629.2		c.813+288G>T		intron	N/A	NP_001153101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC27A2	ENST00000267842.10	TSL:1 MANE Select	c.972+288G>T		intron	N/A	ENSP00000267842.5
	SLC27A2	ENST00000380902.8	TSL:1	c.813+288G>T		intron	N/A	ENSP00000370289.4
	SLC27A2	ENST00000544960.1	TSL:2	c.267+288G>T		intron	N/A	ENSP00000444549.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70193 AN: 151736 Hom.: 17373 Cov.: 31

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.463 AC: 70239 AN: 151854 Hom.: 17388 Cov.: 31 AF XY: 0.464 AC XY: 34427 AN XY: 74204

African (AFR) AF: 0.295 AC: 12205 AN: 41324

American (AMR) AF: 0.450 AC: 6870 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2019 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2285 AN: 5156

South Asian (SAS) AF: 0.387 AC: 1864 AN: 4822

European-Finnish (FIN) AF: 0.617 AC: 6507 AN: 10538

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36804 AN: 67968

Other (OTH) AF: 0.478 AC: 1007 AN: 2108

Alfa AF: 0.509 Hom.: 33553

Bravo AF: 0.442

Asia WGS AF: 0.376 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.71
PhyloP100		-1.6
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: rs2278167; hg19: chr15-50497848;