rs9286331

Variant names:

• chr17-37087798-T-C
• rs9286331
• NM_198834.3:c.7029-359A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-37087798-T-C
• chr17-37087798-T-G

Variant summary

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

The NM_198834.3(ACACA):​c.7029-359A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,058 control chromosomes in the GnomAD database, including 10,544 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 0.32 (10544 hom., cov: 32)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99
• Publications: 3 publications found

Genes affected

ACACA (HGNC:84): (acetyl-CoA carboxylase alpha) Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The enzyme is under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA. Multiple alternatively spliced transcript variants divergent in the 5' sequence and encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACACA Gene-Disease associations (from GenCC):

• acetyl-coa carboxylase deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACA	NM_198834.3	c.7029-359A>G		intron_variant	Intron 55 of 55	ENST00000616317.5	NP_942131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACA	ENST00000616317.5	c.7029-359A>G		intron_variant	Intron 55 of 55	1	NM_198834.3	ENSP00000483300.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48757 AN: 151940 Hom.: 10518 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.321 AC: 48847 AN: 152058 Hom.: 10544 Cov.: 32 AF XY: 0.322 AC XY: 23968 AN XY: 74356

African (AFR) AF: 0.603 AC: 24978 AN: 41444

American (AMR) AF: 0.384 AC: 5872 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3472

East Asian (EAS) AF: 0.312 AC: 1612 AN: 5168

South Asian (SAS) AF: 0.257 AC: 1238 AN: 4822

European-Finnish (FIN) AF: 0.192 AC: 2031 AN: 10584

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11874 AN: 67978

Other (OTH) AF: 0.293 AC: 618 AN: 2110

Alfa AF: 0.274 Hom.: 1008

Bravo AF: 0.349

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.017
DANN	Benign	0.43
PhyloP100		-3.0
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: rs9286331; hg19: chr17-35444733;