rs7886473

Variant names:

• chrX-109679285-A-G
• rs7886473
• NM_001318510.2:c.656-870T>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.656-870T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 110,434 control chromosomes in the GnomAD database, including 8,027 homozygotes. There are 12,964 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 0.41 (8027 hom., 12964 hem., cov: 22)
• Consequence: ACSL4 NM_001318510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL4	NM_001318510.2	c.656-870T>C		intron_variant	Intron 6 of 15	ENST00000672401.1	NP_001305439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL4	ENST00000672401.1	c.656-870T>C		intron_variant	Intron 6 of 15		NM_001318510.2	ENSP00000500273.1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 45110 AN: 110382 Hom.: 8032 Cov.: 22

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.408 AC: 45092 AN: 110434 Hom.: 8027 Cov.: 22 AF XY: 0.396 AC XY: 12964 AN XY: 32718

African (AFR) AF: 0.164 AC: 5010 AN: 30554

American (AMR) AF: 0.312 AC: 3239 AN: 10374

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1512 AN: 2625

East Asian (EAS) AF: 0.0805 AC: 284 AN: 3527

South Asian (SAS) AF: 0.388 AC: 1013 AN: 2612

European-Finnish (FIN) AF: 0.515 AC: 2927 AN: 5684

Middle Eastern (MID) AF: 0.615 AC: 131 AN: 213

European-Non Finnish (NFE) AF: 0.570 AC: 30004 AN: 52671

Other (OTH) AF: 0.449 AC: 676 AN: 1505

Alfa AF: 0.495 Hom.: 47104

Bravo AF: 0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.2
DANN	Benign	0.73
PhyloP100		-0.048
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: rs7886473; hg19: chrX-108922514;