NM_001318510.2:c.-66+3029C>G

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL4	NM_001318510.2	c.-66+3029C>G		intron_variant	Intron 1 of 15	ENST00000672401.1	NP_001305439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL4	ENST00000672401.1	c.-66+3029C>G		intron_variant	Intron 1 of 15		NM_001318510.2	ENSP00000500273.1

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 v4.3

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

Other links and lift over

dbSNP: rs5943427; hg19: chrX-108973339;