rs7887981

Variant names:

• chrX-109652018-T-C
• rs7887981
• NM_001318510.2:c.1855+7336A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318510.2(ACSL4):​c.1855+7336A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 110,944 control chromosomes in the GnomAD database, including 2,029 homozygotes. There are 6,180 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 0.20 (2029 hom., 6180 hem., cov: 22)
• Consequence: ACSL4 NM_001318510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 6 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL4	NM_001318510.2	c.1855+7336A>G		intron_variant	Intron 15 of 15	ENST00000672401.1	NP_001305439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL4	ENST00000672401.1	c.1855+7336A>G		intron_variant	Intron 15 of 15		NM_001318510.2	ENSP00000500273.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 21923 AN: 110885 Hom.: 2028 Cov.: 22

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.000837

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.198 AC: 21915 AN: 110944 Hom.: 2029 Cov.: 22 AF XY: 0.186 AC XY: 6180 AN XY: 33222

African (AFR) AF: 0.0696 AC: 2140 AN: 30741

American (AMR) AF: 0.149 AC: 1552 AN: 10415

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 762 AN: 2630

East Asian (EAS) AF: 0.000839 AC: 3 AN: 3575

South Asian (SAS) AF: 0.0696 AC: 186 AN: 2672

European-Finnish (FIN) AF: 0.275 AC: 1599 AN: 5809

Middle Eastern (MID) AF: 0.341 AC: 74 AN: 217

European-Non Finnish (NFE) AF: 0.287 AC: 15121 AN: 52698

Other (OTH) AF: 0.223 AC: 337 AN: 1514

Alfa AF: 0.249 Hom.: 2029

Bravo AF: 0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.9
DANN	Benign	0.83
PhyloP100		0.10
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: rs7887981; hg19: chrX-108895247;