rs5943418

chrX-109702878-A-GchrX-109702878-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001318510.2(ACSL4):c.-65-6682T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.72 (21813 hom., 22187 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: ACSL4 NM_001318510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BS2: High Homozygotes in GnomAd at 21807 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL4	NM_001318510.2	c.-65-6682T>C		intron_variant		ENST00000672401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL4	ENST00000672401.1	c.-65-6682T>C		intron_variant			NM_001318510.2	P4

Frequencies

GnomAD3 genomes AF: 0.717 AC: 78595 AN: 109584 Hom.: 21807 Cov.: 22 AF XY: 0.695 AC XY: 22141 AN XY: 31840

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.704

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.717 AC: 78640 AN: 109638 Hom.: 21813 Cov.: 22 AF XY: 0.695 AC XY: 22187 AN XY: 31904

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.703

Alfa AF: 0.670 Hom.: 44911

Bravo AF: 0.713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.29
Dann	Benign	0.43

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: rs5943418; hg19: chrX-108946107;