rs749141092

Variant names:

• chr4-184757857-C-G
• NM_001995.5:c.1846G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-184757857-C-G
• chr4-184757857-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001995.5(ACSL1):​c.1846G>C​(p.Gly616Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACSL1 NM_001995.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL1	NM_001995.5	c.1846G>C	p.Gly616Arg	missense_variant	Exon 19 of 21	ENST00000281455.7	NP_001986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL1	ENST00000281455.7	c.1846G>C	p.Gly616Arg	missense_variant	Exon 19 of 21	1	NM_001995.5	ENSP00000281455.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	T;T;D;T;D;.;D;.
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D;.;D;.;D;D;D
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Pathogenic	3.8	.;.;H;.;H;.;H;H
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-6.0	D;.;D;D;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0040	D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D;D
Polyphen		0.95, 0.97	.;.;P;.;P;D;P;.
Vest4		0.73
MutPred		0.50		.;.;Gain of glycosylation at S620 (P = 0.043);.;Gain of glycosylation at S620 (P = 0.043);.;Gain of glycosylation at S620 (P = 0.043);Gain of glycosylation at S620 (P = 0.043);
MVP		0.70
MPC		0.41
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-185679011;