Genetic Variant ACSL5:c.-30+986C>T (chr10-112375255-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_203379.2(ACSL5):c.-30+986C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,864 control chromosomes in the GnomAD database, including 4,110 homozygotes. 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 0.23 ( 4110 hom., cov: 31)

Exomes 𝑓: 0.16 ( 0 hom. )

Consequence

ACSL5
NM_203379.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.470

Publications

29 publications found

Variant links:

Genes affected

ACSL5 (HGNC:16526): (acyl-CoA synthetase long chain family member 5) 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 is highly expressed in uterus and spleen, and in trace amounts in normal brain, but has markedly increased levels in malignant gliomas. This gene functions in mediating fatty acid-induced glioma cell growth. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACSL5 Gene-Disease associations (from GenCC):

diarrhea 13
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACSL5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL5	NM_203379.2 link	c.-30+986C>T		intron_variant	Intron 1 of 20	ENST00000354655.9	NP_976313.1
ACSL5	NM_203380.2 link	c.-317C>T		upstream_gene_variant			NP_976314.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ACSL5	ENST00000354655.9 link	c.-30+986C>T	intron_variant	Intron 1 of 20	2	NM_203379.2	ENSP00000346680.4
ACSL5	ENST00000393081.6 link	c.-317C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 21	5		ENSP00000376796.1
ACSL5	ENST00000393081.6 link	c.-317C>T	5_prime_UTR_variant	Exon 1 of 21	5		ENSP00000376796.1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35107

AN:

151690

Hom.:

4110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.253

GnomAD4 exome

AF:

0.161

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.130

AC:

AN:

Other (OTH)

AF:

0.300

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.231

AC:

35123

AN:

151808

Hom.:

4110

Cov.:

AF XY:

0.231

AC XY:

17119

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.187

AC:

7740

AN:

41392

American (AMR)

AF:

0.205

AC:

3113

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

1062

AN:

3470

East Asian (EAS)

AF:

0.214

AC:

1098

AN:

5140

South Asian (SAS)

AF:

0.220

AC:

1059

AN:

4808

European-Finnish (FIN)

AF:

0.263

AC:

2769

AN:

10542

Middle Eastern (MID)

AF:

0.281

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.257

AC:

17479

AN:

67928

Other (OTH)

AF:

0.255

AC:

537

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1396

2791

4187

5582

6978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.249

Hom.:

18372

Bravo

AF:

0.226

Asia WGS

AF:

0.193

AC:

673

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

(source)

DANN

Benign

0.70

PhyloP100

-0.47

PromoterAI

-0.0082

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over