NM_001995.5:c.-32-1848G>A

Variant names:

• chr4-184805394-C-T
• rs4862423
• NM_001995.5:c.-32-1848G>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.-32-1848G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 797,154 control chromosomes in the GnomAD database, including 59,101 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 0.38 (11781 hom., cov: 32)
  • Exomes 𝑓: 0.39 (47320 hom.)
• Consequence: ACSL1 NM_001995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825
• Publications: 7 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 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.-32-1848G>A		intron	N/A	NP_001986.2
	ACSL1	NM_001286708.2		c.-32-1848G>A		intron	N/A	NP_001273637.1
	ACSL1	NM_001286710.2		c.-33+133G>A		intron	N/A	NP_001273639.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL1	ENST00000281455.7	TSL:1 MANE Select	c.-32-1848G>A		intron	N/A	ENSP00000281455.2
	ACSL1	ENST00000504342.5	TSL:1	c.-32-1848G>A		intron	N/A	ENSP00000425006.1
	ACSL1	ENST00000505492.2	TSL:1	c.-32-1848G>A		intron	N/A	ENSP00000425640.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57486 AN: 151818 Hom.: 11764 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.389 AC: 250768 AN: 645222 Hom.: 47320 Cov.: 8 AF XY: 0.389 AC XY: 117200 AN XY: 301314

African (AFR) AF: 0.227 AC: 2741 AN: 12080

American (AMR) AF: 0.545 AC: 397 AN: 728

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1782 AN: 4040

East Asian (EAS) AF: 0.620 AC: 1661 AN: 2678

South Asian (SAS) AF: 0.487 AC: 6134 AN: 12588

European-Finnish (FIN) AF: 0.355 AC: 76 AN: 214

Middle Eastern (MID) AF: 0.400 AC: 506 AN: 1264

European-Non Finnish (NFE) AF: 0.388 AC: 228859 AN: 590526

Other (OTH) AF: 0.408 AC: 8612 AN: 21104

GnomAD4 genome AF: 0.379 AC: 57527 AN: 151932 Hom.: 11781 Cov.: 32 AF XY: 0.387 AC XY: 28728 AN XY: 74272

African (AFR) AF: 0.244 AC: 10093 AN: 41444

American (AMR) AF: 0.533 AC: 8124 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1625 AN: 3470

East Asian (EAS) AF: 0.640 AC: 3315 AN: 5178

South Asian (SAS) AF: 0.505 AC: 2437 AN: 4826

European-Finnish (FIN) AF: 0.394 AC: 4142 AN: 10516

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26419 AN: 67936

Other (OTH) AF: 0.411 AC: 868 AN: 2112

Alfa AF: 0.388 Hom.: 6331

Bravo AF: 0.387

Asia WGS AF: 0.539 AC: 1871 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.70
PhyloP100		-0.82
PromoterAI		-0.076	Neutral
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: rs4862423; hg19: chr4-185726548;