rs2419621

Positions:

• chr10-112375255-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ACSL5	NM_203379.2	c.-30+986C>T		intron_variant		ENST00000354655.9	NP_976313.1
ACSL5	NM_203380.2	c.-317C>T		upstream_gene_variant			NP_976314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL5	ENST00000354655.9	c.-30+986C>T		intron_variant		2	NM_203379.2	ENSP00000346680.4
ACSL5	ENST00000393081	c.-317C>T		5_prime_UTR_premature_start_codon_gain_variant	1/21	5		ENSP00000376796.1
ACSL5	ENST00000393081	c.-317C>T		5_prime_UTR_variant	1/21	5		ENSP00000376796.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35107 AN: 151690 Hom.: 4110 Cov.: 31

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: 9 AN: 56 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 6 AN XY: 36

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.231 AC: 35123 AN: 151808 Hom.: 4110 Cov.: 31 AF XY: 0.231 AC XY: 17119 AN XY: 74160

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.255

Alfa AF: 0.257 Hom.: 8725

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
DANN	Benign	0.70

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: rs2419621; hg19: chr10-114135013;