4-184795078-T-C

Variant names:

• chr4-184795078-T-C
• rs735949
• NM_001995.5:c.196-6347A>G

Variant summary

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

The NM_001995.5(ACSL1):​c.196-6347A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,248 control chromosomes in the GnomAD database, including 952 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 0.10 (952 hom., cov: 32)
• Consequence: ACSL1 NM_001995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 16 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 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.196-6347A>G		intron	N/A	NP_001986.2
	ACSL1	NM_001286708.2		c.196-6347A>G		intron	N/A	NP_001273637.1
	ACSL1	NM_001286710.2		c.196-6347A>G		intron	N/A	NP_001273639.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL1	ENST00000281455.7	TSL:1 MANE Select	c.196-6347A>G		intron	N/A	ENSP00000281455.2
	ACSL1	ENST00000504342.5	TSL:1	c.196-6347A>G		intron	N/A	ENSP00000425006.1
	ACSL1	ENST00000505492.2	TSL:1	c.196-6347A>G		intron	N/A	ENSP00000425640.2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15390 AN: 152130 Hom.: 953 Cov.: 32

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.101 AC: 15389 AN: 152248 Hom.: 952 Cov.: 32 AF XY: 0.0992 AC XY: 7383 AN XY: 74440

African (AFR) AF: 0.0429 AC: 1783 AN: 41550

American (AMR) AF: 0.103 AC: 1583 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 501 AN: 3466

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0655 AC: 316 AN: 4826

European-Finnish (FIN) AF: 0.0965 AC: 1023 AN: 10602

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9761 AN: 67998

Other (OTH) AF: 0.116 AC: 246 AN: 2116

Alfa AF: 0.121 Hom.: 174

Bravo AF: 0.101

Asia WGS AF: 0.0370 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.43
PhyloP100		-1.3
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: rs735949; hg19: chr4-185716232;