rs5943427

Positions:

• chrX-109730110-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001318510.2(ACSL4):​c.-66+3029C>G 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 0.52 (11077 hom., 16863 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: ACSL4 NM_001318510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL4	NM_001318510.2	c.-66+3029C>G		intron_variant		ENST00000672401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL4	ENST00000672401.1	c.-66+3029C>G		intron_variant			NM_001318510.2	P4

Frequencies

GnomAD3 genomes AF: 0.520 AC: 57676 AN: 110921 Hom.: 11076 Cov.: 23 AF XY: 0.507 AC XY: 16826 AN XY: 33155

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.644

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.531

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: 0.520 AC: 57710 AN: 110974 Hom.: 11077 Cov.: 23 AF XY: 0.508 AC XY: 16863 AN XY: 33218

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.533

Alfa AF: 0.547 Hom.: 4060

Bravo AF: 0.503

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.47

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: rs5943427; hg19: chrX-108973339;