NM_003645.4:c.972+1694A>G

Variant names:

• chr15-50207057-A-G
• rs7162180
• NM_003645.4:c.972+1694A>G

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+1694A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,764 control chromosomes in the GnomAD database, including 10,928 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 0.37 (10928 hom., cov: 31)
• Consequence: SLC27A2 NM_003645.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224
• Publications: 1 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=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC27A2	NM_003645.4	c.972+1694A>G		intron_variant	Intron 4 of 9	ENST00000267842.10	NP_003636.2
SLC27A2	NM_001159629.2	c.813+1694A>G		intron_variant	Intron 3 of 8		NP_001153101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC27A2	ENST00000267842.10	c.972+1694A>G		intron_variant	Intron 4 of 9	1	NM_003645.4	ENSP00000267842.5
SLC27A2	ENST00000380902.8	c.813+1694A>G		intron_variant	Intron 3 of 8	1		ENSP00000370289.4
SLC27A2	ENST00000544960.1	c.267+1694A>G		intron_variant	Intron 5 of 10	2		ENSP00000444549.1
SLC27A2	ENST00000559938.1	n.11+1694A>G		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56538 AN: 151644 Hom.: 10909 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.373 AC: 56593 AN: 151764 Hom.: 10928 Cov.: 31 AF XY: 0.376 AC XY: 27893 AN XY: 74144

African (AFR) AF: 0.448 AC: 18523 AN: 41364

American (AMR) AF: 0.430 AC: 6554 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3466

East Asian (EAS) AF: 0.539 AC: 2769 AN: 5142

South Asian (SAS) AF: 0.434 AC: 2089 AN: 4810

European-Finnish (FIN) AF: 0.350 AC: 3679 AN: 10506

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20937 AN: 67914

Other (OTH) AF: 0.362 AC: 763 AN: 2110

Alfa AF: 0.326 Hom.: 6042

Bravo AF: 0.382

Asia WGS AF: 0.525 AC: 1825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		0.22
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: rs7162180; hg19: chr15-50499254;