chr4-184804262-A-G

Variant names:

• chr4-184804262-A-G
• rs6552828
• NM_001995.5:c.-32-716T>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.-32-716T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,108 control chromosomes in the GnomAD database, including 28,716 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 0.61 (28716 hom., cov: 33)
• Consequence: ACSL1 NM_001995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 27 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL1	NM_001995.5	c.-32-716T>C		intron_variant	Intron 1 of 20	ENST00000281455.7	NP_001986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL1	ENST00000281455.7	c.-32-716T>C		intron_variant	Intron 1 of 20	1	NM_001995.5	ENSP00000281455.2

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92204 AN: 151992 Hom.: 28679 Cov.: 33

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.607 AC: 92282 AN: 152108 Hom.: 28716 Cov.: 33 AF XY: 0.599 AC XY: 44532 AN XY: 74352

African (AFR) AF: 0.713 AC: 29584 AN: 41502

American (AMR) AF: 0.457 AC: 6992 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1814 AN: 3472

East Asian (EAS) AF: 0.359 AC: 1858 AN: 5182

South Asian (SAS) AF: 0.494 AC: 2385 AN: 4824

European-Finnish (FIN) AF: 0.602 AC: 6349 AN: 10548

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.609 AC: 41392 AN: 67976

Other (OTH) AF: 0.575 AC: 1214 AN: 2110

Alfa AF: 0.599 Hom.: 117922

Bravo AF: 0.597

Asia WGS AF: 0.454 AC: 1580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.78
DANN	Benign	0.33
PhyloP100		-1.5
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: rs6552828; hg19: chr4-185725416;