rs13120078

Positions:

• chr4-184810288-G-A
• chr4-184810288-G-C

Variant summary

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

The ENST00000281455.7(ACSL1):​c.-32-6742C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,110 control chromosomes in the GnomAD database, including 6,892 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 0.27 (6892 hom., cov: 32)
• Consequence: ACSL1 ENST00000281455.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490

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 (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSL1	NM_001995.5	c.-32-6742C>T		intron_variant		ENST00000281455.7	NP_001986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL1	ENST00000281455.7	c.-32-6742C>T		intron_variant		1	NM_001995.5	ENSP00000281455	P3

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40502 AN: 151992 Hom.: 6897 Cov.: 32

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.266 AC: 40483 AN: 152110 Hom.: 6892 Cov.: 32 AF XY: 0.262 AC XY: 19482 AN XY: 74360

Gnomad4 AFR AF: 0.0806

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.0740

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.257

Alfa AF: 0.343 Hom.: 12395

Bravo AF: 0.242

Asia WGS AF: 0.156 AC: 542 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	4.3
DANN	Benign	0.67

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: rs13120078; hg19: chr4-185731442;