X-109719433-A-G

Position:

• chrX-109719433-A-G

Variant summary

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

The NM_001318510.2(ACSL4):​c.-66+13706T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 110,751 control chromosomes in the GnomAD database, including 8,851 homozygotes. There are 14,573 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 0.45 (8851 hom., 14573 hem., cov: 23)
• Consequence: ACSL4 NM_001318510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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=-0.92).
• 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/exons	MANE	Protein	UniProt
ACSL4	NM_001318510.2	c.-66+13706T>C		intron_variant		ENST00000672401.1	NP_001305439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL4	ENST00000672401.1	c.-66+13706T>C		intron_variant			NM_001318510.2	ENSP00000500273	P4

Frequencies

GnomAD3 genomes AF: 0.453 AC: 50106 AN: 110697 Hom.: 8854 Cov.: 23 AF XY: 0.442 AC XY: 14552 AN XY: 32929

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.0860

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.453 AC: 50118 AN: 110751 Hom.: 8851 Cov.: 23 AF XY: 0.442 AC XY: 14573 AN XY: 32993

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.0851

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.486

Alfa AF: 0.542 Hom.: 33408

Bravo AF: 0.427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.59

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: rs1324805; hg19: chrX-108962662;