NM_203379.2:c.871-61T>C

Variant names:

• chr10-112411841-T-C
• rs876873
• NM_203379.2:c.871-61T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.82).
• 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 rank	MANE	Protein	UniProt
ACSL5	NM_203379.2	c.871-61T>C		intron_variant	Intron 10 of 20	ENST00000354655.9	NP_976313.1
ACSL5	NM_016234.4	c.1039-61T>C		intron_variant	Intron 10 of 20		NP_057318.2
ACSL5	NM_001387037.1	c.1039-61T>C		intron_variant	Intron 10 of 19		NP_001373966.1
ACSL5	NM_203380.2	c.871-61T>C		intron_variant	Intron 10 of 20		NP_976314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL5	ENST00000354655.9	c.871-61T>C		intron_variant	Intron 10 of 20	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

African (AFR) AF: 0.257 AC: 7811 AN: 30402

American (AMR) AF: 0.0943 AC: 4198 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 2888 AN: 25168

East Asian (EAS) AF: 0.0215 AC: 840 AN: 39100

South Asian (SAS) AF: 0.121 AC: 10107 AN: 83378

European-Finnish (FIN) AF: 0.131 AC: 6914 AN: 52846

Middle Eastern (MID) AF: 0.222 AC: 1213 AN: 5466

European-Non Finnish (NFE) AF: 0.159 AC: 156929 AN: 987952

Other (OTH) AF: 0.145 AC: 8122 AN: 55944

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

African (AFR) AF: 0.248 AC: 10265 AN: 41446

American (AMR) AF: 0.139 AC: 2123 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3470

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5194

South Asian (SAS) AF: 0.118 AC: 571 AN: 4822

European-Finnish (FIN) AF: 0.126 AC: 1333 AN: 10598

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10736 AN: 67966

Other (OTH) AF: 0.176 AC: 372 AN: 2112

Alfa AF: 0.160 Hom.: 3775

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
PhyloP100		0.065
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: rs876873; hg19: chr10-114171599;