4-184805394-C-T

Position:

• chr4-184805394-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACSL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSL1	NM_001995.5	c.-32-1848G>A		intron_variant		ENST00000281455.7	NP_001986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL1	ENST00000281455.7	c.-32-1848G>A		intron_variant		1	NM_001995.5	ENSP00000281455.2

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

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.441

Gnomad4 EAS exome AF: 0.620

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.355

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.408

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

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.411

Alfa AF: 0.382 Hom.: 3910

Bravo AF: 0.387

Asia WGS AF: 0.539 AC: 1871 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs4862423; hg19: chr4-185726548;