rs13126272

Variant names:

• chr4-184810786-G-T
• rs13126272
• NM_001995.5:c.-32-7240C>A

Variant summary

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

The NM_001995.5(ACSL1):​c.-32-7240C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,050 control chromosomes in the GnomAD database, including 7,570 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 0.31 (7570 hom., cov: 32)
• Consequence: ACSL1 NM_001995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 10 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001995.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL1	NM_001995.5	MANE Select	c.-32-7240C>A		intron	N/A	NP_001986.2
	ACSL1	NM_001286708.2		c.-33+1374C>A		intron	N/A	NP_001273637.1
	ACSL1	NM_001381877.1		c.-33+3127C>A		intron	N/A	NP_001368806.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL1	ENST00000281455.7	TSL:1 MANE Select	c.-32-7240C>A		intron	N/A	ENSP00000281455.2
	ACSL1	ENST00000504342.5	TSL:1	c.-33+1374C>A		intron	N/A	ENSP00000425006.1
	ACSL1	ENST00000505492.2	TSL:1	c.-32-7240C>A		intron	N/A	ENSP00000425640.2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47002 AN: 151932 Hom.: 7556 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.309 AC: 47037 AN: 152050 Hom.: 7570 Cov.: 32 AF XY: 0.301 AC XY: 22401 AN XY: 74316

African (AFR) AF: 0.346 AC: 14344 AN: 41448

American (AMR) AF: 0.248 AC: 3785 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 986 AN: 3466

East Asian (EAS) AF: 0.105 AC: 542 AN: 5166

South Asian (SAS) AF: 0.262 AC: 1261 AN: 4818

European-Finnish (FIN) AF: 0.283 AC: 2992 AN: 10570

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22185 AN: 67986

Other (OTH) AF: 0.281 AC: 592 AN: 2110

Alfa AF: 0.322 Hom.: 3231

Bravo AF: 0.306

Asia WGS AF: 0.185 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.072
DANN	Benign	0.58
PhyloP100		-2.1
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: rs13126272; hg19: chr4-185731940;