NM_001995.5:c.-32-6742C>T

Variant names:

• chr4-184810288-G-A
• rs13120078
• NM_001995.5:c.-32-6742C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001995.5(ACSL1):​c.-32-6742C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,110 control chromosomes in the GnomAD database, including 6,892 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 0.27 (6892 hom., cov: 32)
• Consequence: ACSL1 NM_001995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490
• Publications: 11 publications found

Genes affected

ACSL1 (HGNC:3569): (acyl-CoA synthetase long chain family member 1) 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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL1	NM_001995.5	c.-32-6742C>T		intron_variant	Intron 1 of 20	ENST00000281455.7	NP_001986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL1	ENST00000281455.7	c.-32-6742C>T		intron_variant	Intron 1 of 20	1	NM_001995.5	ENSP00000281455.2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40502 AN: 151992 Hom.: 6897 Cov.: 32

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.266 AC: 40483 AN: 152110 Hom.: 6892 Cov.: 32 AF XY: 0.262 AC XY: 19482 AN XY: 74360

African (AFR) AF: 0.0806 AC: 3349 AN: 41538

American (AMR) AF: 0.215 AC: 3285 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1074 AN: 3468

East Asian (EAS) AF: 0.0740 AC: 383 AN: 5174

South Asian (SAS) AF: 0.271 AC: 1308 AN: 4832

European-Finnish (FIN) AF: 0.395 AC: 4168 AN: 10546

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25966 AN: 67956

Other (OTH) AF: 0.257 AC: 541 AN: 2106

Alfa AF: 0.335 Hom.: 15170

Bravo AF: 0.242

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.67
PhyloP100		-0.49
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: rs13120078; hg19: chr4-185731442;