Genetic Variant ACSL4:c.*158G>A (chrX-109643871-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001318510.2(ACSL4):c.*158G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00992 in 614,092 control chromosomes in the GnomAD database, including 68 homozygotes. There are 1,996 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 0.015 ( 24 hom., 500 hem., cov: 23)

Exomes 𝑓: 0.0089 ( 44 hom. 1496 hem. )

Consequence

ACSL4
NM_001318510.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.232

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0147 (1648/111948) while in subpopulation EAS AF= 0.0555 (199/3587). AF 95% confidence interval is 0.0492. There are 24 homozygotes in gnomad4. There are 500 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL4	NM_001318510.2 link	c.*158G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000672401.1	NP_001305439.1	O60488-2Q8TAF6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL4	ENST00000672401 link	c.*158G>A		3_prime_UTR_variant	Exon 16 of 16		NM_001318510.2	ENSP00000500273.1		O60488-2

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

1642

AN:

111892

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

498

AN XY:

34128

show subpopulations

Gnomad AFR

AF:

0.0328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.000377

Gnomad EAS

AF:

0.0553

Gnomad SAS

AF:

0.0258

Gnomad FIN

AF:

0.000166

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.00369

Gnomad OTH

AF:

0.0127

GnomAD4 exome

AF:

0.00885

AC:

4446

AN:

502144

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

1496

AN XY:

144462

show subpopulations

Gnomad4 AFR exome

AF:

0.0307

Gnomad4 AMR exome

AF:

0.0236

Gnomad4 ASJ exome

AF:

0.000150

Gnomad4 EAS exome

AF:

0.0436

Gnomad4 SAS exome

AF:

0.0261

Gnomad4 FIN exome

AF:

0.000190

Gnomad4 NFE exome

AF:

0.00359

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.0147

AC:

1648

AN:

111948

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

500

AN XY:

34194

show subpopulations

Gnomad4 AFR

AF:

0.0328

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.000377

Gnomad4 EAS

AF:

0.0555

Gnomad4 SAS

AF:

0.0266

Gnomad4 FIN

AF:

0.000166

Gnomad4 NFE

AF:

0.00369

Gnomad4 OTH

AF:

0.0125

Alfa

AF:

0.00977

Hom.:

Bravo

AF:

0.0161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.82

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.97

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over