rs12453407

chr17-37232521-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ACACA	NM_198834.3	c.3246+2454T>C		intron_variant		ENST00000616317.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACACA	ENST00000616317.5	c.3246+2454T>C		intron_variant		1	NM_198834.3

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

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.609

Alfa AF: 0.500 Hom.: 18351

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12453407; hg19: chr17-35589436;