rs12856122

Variant names:

• chrX-109719340-T-G
• rs12856122
• NM_001318510.2:c.-66+13799A>C

Variant summary

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

The ENST00000672401.1(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 ENST00000672401.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000672401.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL4	NM_001318510.2	MANE Select	c.-66+13799A>C		intron	N/A	NP_001305439.1
	ACSL4	NM_001318509.2		c.-234+13799A>C		intron	N/A	NP_001305438.1
	ACSL4	NM_001437245.1		c.-120+13799A>C		intron	N/A	NP_001424174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL4	ENST00000672401.1	MANE Select	c.-66+13799A>C		intron	N/A	ENSP00000500273.1
	ACSL4	ENST00000348502.10	TSL:1	c.-63+13799A>C		intron	N/A	ENSP00000262835.7
	ACSL4	ENST00000340800.7	TSL:5	c.-252+13799A>C		intron	N/A	ENSP00000339787.2

Frequencies

GnomAD3 genomes AF: 0.411 AC: 45157 AN: 109979 Hom.: 8024 Cov.: 22

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

African (AFR) AF: 0.170 AC: 5155 AN: 30319

American (AMR) AF: 0.315 AC: 3276 AN: 10397

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1502 AN: 2610

East Asian (EAS) AF: 0.0840 AC: 297 AN: 3534

South Asian (SAS) AF: 0.382 AC: 967 AN: 2529

European-Finnish (FIN) AF: 0.520 AC: 2974 AN: 5720

Middle Eastern (MID) AF: 0.601 AC: 125 AN: 208

European-Non Finnish (NFE) AF: 0.569 AC: 29881 AN: 52540

Other (OTH) AF: 0.446 AC: 673 AN: 1509

Alfa AF: 0.509 Hom.: 31962

Bravo AF: 0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.85
PhyloP100		-0.24
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: rs12856122; hg19: chrX-108962569;