rs9330250

Variant names:

• chr17-37220433-T-C
• rs9330250
• NM_198834.3:c.3683+1291A>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.3683+1291A>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 151,980 control chromosomes in the GnomAD database, including 9,548 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 (9548 hom., cov: 31)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722
• Publications: 5 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=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACA	NM_198834.3	c.3683+1291A>G		intron_variant	Intron 29 of 55	ENST00000616317.5	NP_942131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACA	ENST00000616317.5	c.3683+1291A>G		intron_variant	Intron 29 of 55	1	NM_198834.3	ENSP00000483300.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48656 AN: 151864 Hom.: 9527 Cov.: 31

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.204

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: 48735 AN: 151980 Hom.: 9548 Cov.: 31 AF XY: 0.320 AC XY: 23761 AN XY: 74306

African (AFR) AF: 0.537 AC: 22218 AN: 41396

American (AMR) AF: 0.397 AC: 6070 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3468

East Asian (EAS) AF: 0.305 AC: 1575 AN: 5158

South Asian (SAS) AF: 0.259 AC: 1248 AN: 4812

European-Finnish (FIN) AF: 0.229 AC: 2424 AN: 10574

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13875 AN: 67984

Other (OTH) AF: 0.293 AC: 618 AN: 2112

Alfa AF: 0.242 Hom.: 2914

Bravo AF: 0.345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
PhyloP100		0.72

Splicing

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

Other links and lift over

dbSNP: rs9330250; hg19: chr17-35577350;