rs10749118

Positions:

• chr10-112389721-C-A
• chr10-112389721-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.-29-5197C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,858 control chromosomes in the GnomAD database, including 18,961 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 0.50 (18961 hom., cov: 31)
• Consequence: ACSL5 NM_203379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSL5	NM_203379.2	c.-29-5197C>A		intron_variant		ENST00000354655.9	NP_976313.1
ACSL5	NM_001387037.1	c.140-5197C>A		intron_variant			NP_001373966.1
ACSL5	NM_016234.4	c.140-5197C>A		intron_variant			NP_057318.2
ACSL5	NM_203380.2	c.-29-5197C>A		intron_variant			NP_976314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL5	ENST00000354655.9	c.-29-5197C>A		intron_variant		2	NM_203379.2	ENSP00000346680	P1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75721 AN: 151740 Hom.: 18955 Cov.: 31

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.499 AC: 75772 AN: 151858 Hom.: 18961 Cov.: 31 AF XY: 0.500 AC XY: 37067 AN XY: 74180

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.485

Alfa AF: 0.384 Hom.: 1046

Bravo AF: 0.499

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.20
DANN	Benign	0.33

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: rs10749118; hg19: chr10-114149479;