X-109719433-A-G

Variant names:

• chrX-109719433-A-G
• rs1324805
• NM_001318510.2:c.-66+13706T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACSL4	NM_001318510.2	c.-66+13706T>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.-66+13706T>C		intron_variant	Intron 1 of 15		NM_001318510.2	ENSP00000500273.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 50106 AN: 110697 Hom.: 8854 Cov.: 23

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

African (AFR) AF: 0.312 AC: 9483 AN: 30419

American (AMR) AF: 0.332 AC: 3473 AN: 10456

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1507 AN: 2626

East Asian (EAS) AF: 0.0851 AC: 302 AN: 3549

South Asian (SAS) AF: 0.388 AC: 1031 AN: 2660

European-Finnish (FIN) AF: 0.517 AC: 3006 AN: 5818

Middle Eastern (MID) AF: 0.614 AC: 132 AN: 215

European-Non Finnish (NFE) AF: 0.571 AC: 30151 AN: 52819

Other (OTH) AF: 0.486 AC: 737 AN: 1516

Alfa AF: 0.529 Hom.: 41922

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
PhyloP100		-1.0
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: rs1324805; hg19: chrX-108962662;