chr4-184816689-G-A

Variant names:

• chr4-184816689-G-A
• rs9997745
• NM_001995.5:c.-33+9227C>T

Variant summary

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

The NM_001995.5(ACSL1):​c.-33+9227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,948 control chromosomes in the GnomAD database, including 7,125 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 0.24 (7125 hom., cov: 32)
• Consequence: ACSL1 NM_001995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 17 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]

ENSG00000251139 (HGNC:):

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 = 0.533 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.-33+9227C>T		intron	N/A	NP_001986.2
	ACSL1	NM_001381877.1		c.-97-2712C>T		intron	N/A	NP_001368806.1
	ACSL1	NM_001381878.1		c.-33+8477C>T		intron	N/A	NP_001368807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL1	ENST00000281455.7	TSL:1 MANE Select	c.-33+9227C>T		intron	N/A	ENSP00000281455.2
	ACSL1	ENST00000505492.2	TSL:1	c.-33+9227C>T		intron	N/A	ENSP00000425640.2
	ACSL1	ENST00000515030.5	TSL:5	c.-33+9836C>T		intron	N/A	ENSP00000422607.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36777 AN: 151830 Hom.: 7100 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0718

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.243 AC: 36850 AN: 151948 Hom.: 7125 Cov.: 32 AF XY: 0.237 AC XY: 17622 AN XY: 74258

African (AFR) AF: 0.539 AC: 22314 AN: 41412

American (AMR) AF: 0.143 AC: 2181 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0715 AC: 344 AN: 4812

European-Finnish (FIN) AF: 0.116 AC: 1221 AN: 10538

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9773 AN: 67966

Other (OTH) AF: 0.209 AC: 441 AN: 2110

Alfa AF: 0.182 Hom.: 4385

Bravo AF: 0.259

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.2
DANN	Benign	0.57
PhyloP100		0.27
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: rs9997745; hg19: chr4-185737843;