rs5943427

Variant names:

• chrX-109730110-G-C
• rs5943427
• NM_001318510.2:c.-66+3029C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001318510.2(ACSL4):​c.-66+3029C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.52 (11077 hom., 16863 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: ACSL4 NM_001318510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 2 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: Orphanet, ClinGen, Illumina
• intellectual disability, X-linked 63

  Inheritance: XL Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318510.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL4	NM_001318510.2	MANE Select	c.-66+3029C>G		intron	N/A	NP_001305439.1	O60488-2
	ACSL4	NM_001318509.2		c.-234+3029C>G		intron	N/A	NP_001305438.1	O60488-1
	ACSL4	NM_001437245.1		c.-120+3029C>G		intron	N/A	NP_001424174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL4	ENST00000672401.1	MANE Select	c.-66+3029C>G		intron	N/A	ENSP00000500273.1	O60488-2
	ACSL4	ENST00000348502.10	TSL:1	c.-63+3029C>G		intron	N/A	ENSP00000262835.7	O60488-2
	ACSL4	ENST00000340800.7	TSL:5	c.-252+3029C>G		intron	N/A	ENSP00000339787.2	O60488-1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 57676 AN: 110921 Hom.: 11076 Cov.: 23

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.644

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.531

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.520 AC: 57710 AN: 110974 Hom.: 11077 Cov.: 23 AF XY: 0.508 AC XY: 16863 AN XY: 33218

African (AFR) AF: 0.524 AC: 15993 AN: 30508

American (AMR) AF: 0.370 AC: 3881 AN: 10478

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1511 AN: 2629

East Asian (EAS) AF: 0.148 AC: 525 AN: 3546

South Asian (SAS) AF: 0.422 AC: 1136 AN: 2689

European-Finnish (FIN) AF: 0.516 AC: 3003 AN: 5815

Middle Eastern (MID) AF: 0.653 AC: 139 AN: 213

European-Non Finnish (NFE) AF: 0.575 AC: 30419 AN: 52914

Other (OTH) AF: 0.533 AC: 807 AN: 1514

Alfa AF: 0.547 Hom.: 4060

Bravo AF: 0.503

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.47
PhyloP100		-0.15
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5943427;

hg19: chrX-108973339;