rs12453407

Variant names:

• chr17-37232521-A-G
• rs12453407
• NM_198834.3:c.3246+2454T>C

Variant summary

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

The NM_198834.3(ACACA):​c.3246+2454T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,056 control chromosomes in the GnomAD database, including 34,706 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 0.65 (34706 hom., cov: 31)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACA	NM_198834.3	c.3246+2454T>C		intron_variant	Intron 25 of 55	ENST00000616317.5	NP_942131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACA	ENST00000616317.5	c.3246+2454T>C		intron_variant	Intron 25 of 55	1	NM_198834.3	ENSP00000483300.1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98093 AN: 151938 Hom.: 34633 Cov.: 31

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.646 AC: 98228 AN: 152056 Hom.: 34706 Cov.: 31 AF XY: 0.653 AC XY: 48548 AN XY: 74330

African (AFR) AF: 0.904 AC: 37491 AN: 41492

American (AMR) AF: 0.689 AC: 10524 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1422 AN: 3468

East Asian (EAS) AF: 0.987 AC: 5104 AN: 5172

South Asian (SAS) AF: 0.699 AC: 3367 AN: 4818

European-Finnish (FIN) AF: 0.600 AC: 6346 AN: 10572

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32199 AN: 67948

Other (OTH) AF: 0.609 AC: 1287 AN: 2112

Alfa AF: 0.523 Hom.: 27042

Bravo AF: 0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.61
PhyloP100		-0.14

Splicing

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

Other links and lift over

dbSNP: rs12453407; hg19: chr17-35589436;