NM_001995.5:c.-33+982C>A

Variant names:

• chr4-184824934-G-T
• rs12503643
• NM_001995.5:c.-33+982C>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.-33+982C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,056 control chromosomes in the GnomAD database, including 18,601 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 0.48 (18601 hom., cov: 32)
• Consequence: ACSL1 NM_001995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL1	NM_001995.5	MANE Select	c.-33+982C>A		intron	N/A	NP_001986.2
	ACSL1	NM_001381877.1		c.-98+982C>A		intron	N/A	NP_001368806.1	P33121-1
	ACSL1	NM_001381878.1		c.-33+232C>A		intron	N/A	NP_001368807.1	P33121-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL1	ENST00000281455.7	TSL:1 MANE Select	c.-33+982C>A		intron	N/A	ENSP00000281455.2	P33121-1
	ACSL1	ENST00000505492.2	TSL:1	c.-33+982C>A		intron	N/A	ENSP00000425640.2	H0Y9Z9
	ACSL1	ENST00000515030.5	TSL:5	c.-33+1591C>A		intron	N/A	ENSP00000422607.1	P33121-1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72276 AN: 151938 Hom.: 18573 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.476 AC: 72358 AN: 152056 Hom.: 18601 Cov.: 32 AF XY: 0.472 AC XY: 35071 AN XY: 74320

African (AFR) AF: 0.686 AC: 28444 AN: 41456

American (AMR) AF: 0.394 AC: 6019 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1467 AN: 3470

East Asian (EAS) AF: 0.520 AC: 2694 AN: 5176

South Asian (SAS) AF: 0.402 AC: 1939 AN: 4822

European-Finnish (FIN) AF: 0.324 AC: 3421 AN: 10560

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26955 AN: 67986

Other (OTH) AF: 0.445 AC: 938 AN: 2110

Alfa AF: 0.427 Hom.: 34306

Bravo AF: 0.495

Asia WGS AF: 0.493 AC: 1718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.49
PhyloP100		-0.24
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: rs12503643; hg19: chr4-185746088;