rs1365508

Positions:

• chr15-50208787-G-A
• chr15-50208787-G-C

Variant summary

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

The NM_003645.4(SLC27A2):​c.972+3424G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,010 control chromosomes in the GnomAD database, including 12,944 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 0.40 (12944 hom., cov: 32)
• Consequence: SLC27A2 NM_003645.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC27A2	NM_003645.4	c.972+3424G>A		intron_variant		ENST00000267842.10	NP_003636.2
SLC27A2	NM_001159629.2	c.813+3424G>A		intron_variant			NP_001153101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC27A2	ENST00000267842.10	c.972+3424G>A		intron_variant		1	NM_003645.4	ENSP00000267842	P1
SLC27A2	ENST00000380902.8	c.813+3424G>A		intron_variant		1		ENSP00000370289
SLC27A2	ENST00000544960.1	c.267+3424G>A		intron_variant		2		ENSP00000444549
SLC27A2	ENST00000559938.1	n.11+3424G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60671 AN: 151892 Hom.: 12940 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.399 AC: 60703 AN: 152010 Hom.: 12944 Cov.: 32 AF XY: 0.391 AC XY: 29050 AN XY: 74274

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.0365

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.423

Alfa AF: 0.458 Hom.: 21612

Bravo AF: 0.395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.60

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: rs1365508; hg19: chr15-50500984;