rs876873

Positions:

• chr10-112411841-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203379.2(ACSL5):​c.871-61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,476,868 control chromosomes in the GnomAD database, including 18,548 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 0.17 (2510 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16038 hom.)
• Consequence: ACSL5 NM_203379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSL5	NM_203379.2	c.871-61T>C		intron_variant		ENST00000354655.9	NP_976313.1
ACSL5	NM_016234.4	c.1039-61T>C		intron_variant			NP_057318.2
ACSL5	NM_001387037.1	c.1039-61T>C		intron_variant			NP_001373966.1
ACSL5	NM_203380.2	c.871-61T>C		intron_variant			NP_976314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL5	ENST00000354655.9	c.871-61T>C		intron_variant		2	NM_203379.2	ENSP00000346680.4

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26029 AN: 151998 Hom.: 2509 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0113

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.150 AC: 199022 AN: 1324752 Hom.: 16038 AF XY: 0.149 AC XY: 99591 AN XY: 666364

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.0943

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.0215

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.171 AC: 26035 AN: 152116 Hom.: 2510 Cov.: 32 AF XY: 0.166 AC XY: 12335 AN XY: 74394

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0114

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.176

Alfa AF: 0.158 Hom.: 2585

Bravo AF: 0.173

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs876873; hg19: chr10-114171599;