rs4862417

Variant names:

• chr4-184769447-A-G
• rs4862417
• NM_001995.5:c.993+952T>C

Variant summary

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

The NM_001995.5(ACSL1):​c.993+952T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,186 control chromosomes in the GnomAD database, including 7,177 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 0.29 (7177 hom., cov: 32)
• Consequence: ACSL1 NM_001995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714
• Publications: 11 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 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.993+952T>C		intron	N/A	NP_001986.2
	ACSL1	NM_001286708.2		c.993+952T>C		intron	N/A	NP_001273637.1	P33121-1
	ACSL1	NM_001286710.2		c.993+808T>C		intron	N/A	NP_001273639.1	P33121-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL1	ENST00000281455.7	TSL:1 MANE Select	c.993+952T>C		intron	N/A	ENSP00000281455.2	P33121-1
	ACSL1	ENST00000504342.5	TSL:1	c.993+952T>C		intron	N/A	ENSP00000425006.1	P33121-1
	ACSL1	ENST00000505492.2	TSL:1	c.916-997T>C		intron	N/A	ENSP00000425640.2	H0Y9Z9

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43964 AN: 152068 Hom.: 7162 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.289 AC: 44015 AN: 152186 Hom.: 7177 Cov.: 32 AF XY: 0.296 AC XY: 22005 AN XY: 74404

African (AFR) AF: 0.270 AC: 11200 AN: 41542

American (AMR) AF: 0.431 AC: 6589 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3470

East Asian (EAS) AF: 0.683 AC: 3527 AN: 5162

South Asian (SAS) AF: 0.388 AC: 1869 AN: 4822

European-Finnish (FIN) AF: 0.255 AC: 2697 AN: 10590

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16569 AN: 67990

Other (OTH) AF: 0.315 AC: 666 AN: 2114

Alfa AF: 0.265 Hom.: 25537

Bravo AF: 0.302

Asia WGS AF: 0.531 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.1
DANN	Benign	0.72
PhyloP100		0.71
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: rs4862417; hg19: chr4-185690601;