rs5943418

Variant names:

• chrX-109702878-A-G
• rs5943418
• NM_001318510.2:c.-65-6682T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-109702878-A-G
• chrX-109702878-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

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
• Publications: 2 publications found

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]

ACSL4 Gene-Disease associations (from GenCC):

• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: ClinGen, Illumina, Orphanet
• intellectual disability, X-linked 63

  Inheritance: XL Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL4	NM_001318510.2	c.-65-6682T>C		intron_variant	Intron 1 of 15	ENST00000672401.1	NP_001305439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL4	ENST00000672401.1	c.-65-6682T>C		intron_variant	Intron 1 of 15		NM_001318510.2	ENSP00000500273.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 78595 AN: 109584 Hom.: 21807 Cov.: 22

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

African (AFR) AF: 0.947 AC: 28485 AN: 30091

American (AMR) AF: 0.479 AC: 4891 AN: 10211

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 1773 AN: 2622

East Asian (EAS) AF: 0.151 AC: 537 AN: 3561

South Asian (SAS) AF: 0.472 AC: 1218 AN: 2578

European-Finnish (FIN) AF: 0.642 AC: 3607 AN: 5615

Middle Eastern (MID) AF: 0.770 AC: 164 AN: 213

European-Non Finnish (NFE) AF: 0.693 AC: 36425 AN: 52582

Other (OTH) AF: 0.703 AC: 1054 AN: 1499

Alfa AF: 0.680 Hom.: 60262

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
PhyloP100		-0.73
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: rs5943418; hg19: chrX-108946107;