NM_203379.2:c.-30+5869G>A

Variant names:

• chr10-112380138-G-A
• rs1926564
• NM_203379.2:c.-30+5869G>A

Variant summary

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

The NM_203379.2(ACSL5):​c.-30+5869G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,140 control chromosomes in the GnomAD database, including 60,990 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 0.89 (60990 hom., cov: 31)
• Consequence: ACSL5 NM_203379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 5 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL5	NM_203379.2	c.-30+5869G>A		intron_variant	Intron 1 of 20	ENST00000354655.9	NP_976313.1
ACSL5	NM_016234.4	c.139+3690G>A		intron_variant	Intron 1 of 20		NP_057318.2
ACSL5	NM_001387037.1	c.139+3690G>A		intron_variant	Intron 1 of 19		NP_001373966.1
ACSL5	NM_203380.2	c.-30+4596G>A		intron_variant	Intron 1 of 20		NP_976314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL5	ENST00000354655.9	c.-30+5869G>A		intron_variant	Intron 1 of 20	2	NM_203379.2	ENSP00000346680.4

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136039 AN: 152022 Hom.: 60952 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.895 AC: 136131 AN: 152140 Hom.: 60990 Cov.: 31 AF XY: 0.894 AC XY: 66456 AN XY: 74352

African (AFR) AF: 0.880 AC: 36525 AN: 41506

American (AMR) AF: 0.874 AC: 13349 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3372 AN: 3472

East Asian (EAS) AF: 0.963 AC: 4966 AN: 5156

South Asian (SAS) AF: 0.958 AC: 4620 AN: 4822

European-Finnish (FIN) AF: 0.831 AC: 8797 AN: 10582

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61527 AN: 68006

Other (OTH) AF: 0.910 AC: 1919 AN: 2108

Alfa AF: 0.909 Hom.: 125492

Bravo AF: 0.896

Asia WGS AF: 0.944 AC: 3284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.0
DANN	Benign	0.59
PhyloP100		-0.053
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: rs1926564; hg19: chr10-114139896;