rs745805

chr4-184796978-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001995.5(ACSL1):c.195+6342T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,072 control chromosomes in the GnomAD database, including 7,522 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 0.28 (7522 hom., cov: 32)
• Consequence: ACSL1 NM_001995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL1	NM_001995.5	c.195+6342T>A		intron_variant		ENST00000281455.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL1	ENST00000281455.7	c.195+6342T>A		intron_variant		1	NM_001995.5	P3

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42146 AN: 151954 Hom.: 7492 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.278 AC: 42227 AN: 152072 Hom.: 7522 Cov.: 32 AF XY: 0.275 AC XY: 20465 AN XY: 74328

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.259

Alfa AF: 0.241 Hom.: 721

Bravo AF: 0.293

Asia WGS AF: 0.258 AC: 899 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	0.60
Dann	Benign	0.46

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: rs745805; hg19: chr4-185718132;