rs2419627

Variant names:

• chr10-112407545-C-T
• rs2419627
• NM_203379.2:c.433-877C>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.433-877C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,910 control chromosomes in the GnomAD database, including 3,668 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 0.20 (3668 hom., cov: 31)
• Consequence: ACSL5 NM_203379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• 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=-1.09).
• 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.433-877C>T		intron_variant	Intron 5 of 20	ENST00000354655.9	NP_976313.1
ACSL5	NM_016234.4	c.601-877C>T		intron_variant	Intron 5 of 20		NP_057318.2
ACSL5	NM_001387037.1	c.601-877C>T		intron_variant	Intron 5 of 19		NP_001373966.1
ACSL5	NM_203380.2	c.433-877C>T		intron_variant	Intron 5 of 20		NP_976314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL5	ENST00000354655.9	c.433-877C>T		intron_variant	Intron 5 of 20	2	NM_203379.2	ENSP00000346680.4

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30445 AN: 151792 Hom.: 3668 Cov.: 31

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.200 AC: 30452 AN: 151910 Hom.: 3668 Cov.: 31 AF XY: 0.203 AC XY: 15097 AN XY: 74216

African (AFR) AF: 0.0594 AC: 2463 AN: 41472

American (AMR) AF: 0.198 AC: 3010 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1113 AN: 5142

South Asian (SAS) AF: 0.231 AC: 1111 AN: 4812

European-Finnish (FIN) AF: 0.315 AC: 3316 AN: 10522

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.258 AC: 17546 AN: 67946

Other (OTH) AF: 0.228 AC: 480 AN: 2106

Alfa AF: 0.235 Hom.: 2457

Bravo AF: 0.186

Asia WGS AF: 0.209 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.42
DANN	Benign	0.57
PhyloP100		-1.8
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: rs2419627; hg19: chr10-114167303;