10-112396983-G-T

Variant names:

• chr10-112396983-G-T
• rs17129754
• NM_203379.2:c.156+1881G>T

Variant summary

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

The NM_203379.2(ACSL5):​c.156+1881G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,874 control chromosomes in the GnomAD database, including 3,946 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 0.22 (3946 hom., cov: 31)
• Consequence: ACSL5 NM_203379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 8 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)

ENSG00000232934 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL5	NM_203379.2	c.156+1881G>T		intron_variant	Intron 2 of 20	ENST00000354655.9	NP_976313.1
ACSL5	NM_016234.4	c.324+1881G>T		intron_variant	Intron 2 of 20		NP_057318.2
ACSL5	NM_001387037.1	c.324+1881G>T		intron_variant	Intron 2 of 19		NP_001373966.1
ACSL5	NM_203380.2	c.156+1881G>T		intron_variant	Intron 2 of 20		NP_976314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL5	ENST00000354655.9	c.156+1881G>T		intron_variant	Intron 2 of 20	2	NM_203379.2	ENSP00000346680.4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33869 AN: 151756 Hom.: 3946 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.223 AC: 33883 AN: 151874 Hom.: 3946 Cov.: 31 AF XY: 0.223 AC XY: 16579 AN XY: 74226

African (AFR) AF: 0.148 AC: 6126 AN: 41420

American (AMR) AF: 0.214 AC: 3257 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1170 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1114 AN: 5158

South Asian (SAS) AF: 0.231 AC: 1114 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2754 AN: 10516

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17565 AN: 67934

Other (OTH) AF: 0.251 AC: 529 AN: 2104

Alfa AF: 0.199 Hom.: 1324

Bravo AF: 0.216

Asia WGS AF: 0.217 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.62
PhyloP100		-1.3
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: rs17129754; hg19: chr10-114156741;