NM_001318510.2:c.-12-625A>G

Variant names:

• chrX-109684000-T-C
• rs5943414
• NM_001318510.2:c.-12-625A>G

Variant summary

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

The NM_001318510.2(ACSL4):​c.-12-625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 110,723 control chromosomes in the GnomAD database, including 8,036 homozygotes. There are 13,054 hemizygotes in GnomAD. 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 0.41 (8036 hom., 13054 hem., cov: 23)
• Consequence: ACSL4 NM_001318510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410

Genes affected

ACSL4 (HGNC:3571): (acyl-CoA synthetase long chain family member 4) The protein encoded by this gene is an isozyme of the 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 preferentially utilizes arachidonate as substrate. The absence of this enzyme may contribute to the cognitive disability or Alport syndrome. Alternative splicing of this gene generates multiple transcript variants. [provided by RefSeq, Jan 2016]

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 = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL4	NM_001318510.2	c.-12-625A>G		intron_variant	Intron 2 of 15	ENST00000672401.1	NP_001305439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL4	ENST00000672401.1	c.-12-625A>G		intron_variant	Intron 2 of 15		NM_001318510.2	ENSP00000500273.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 45204 AN: 110669 Hom.: 8041 Cov.: 23 AF XY: 0.397 AC XY: 13052 AN XY: 32893

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.622

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.408 AC: 45185 AN: 110723 Hom.: 8036 Cov.: 23 AF XY: 0.396 AC XY: 13054 AN XY: 32957

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.0805

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.450

Alfa AF: 0.527 Hom.: 13278

Bravo AF: 0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.50

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: rs5943414; hg19: chrX-108927229;