rs12856122

Positions:

• chrX-109719340-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318510.2(ACSL4):​c.-66+13799A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 110,035 control chromosomes in the GnomAD database, including 8,019 homozygotes. There are 12,950 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 (8019 hom., 12950 hem., cov: 22)
• Consequence: ACSL4 NM_001318510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL4	NM_001318510.2	c.-66+13799A>C		intron_variant		ENST00000672401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL4	ENST00000672401.1	c.-66+13799A>C		intron_variant			NM_001318510.2	P4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 45157 AN: 109979 Hom.: 8024 Cov.: 22 AF XY: 0.401 AC XY: 12944 AN XY: 32275

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.607

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.410 AC: 45144 AN: 110035 Hom.: 8019 Cov.: 22 AF XY: 0.400 AC XY: 12950 AN XY: 32341

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.0840

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.446

Alfa AF: 0.533 Hom.: 25717

Bravo AF: 0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.85

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: rs12856122; hg19: chrX-108962569;