rs2287352

Variant names:

• chr17-37248370-T-C
• rs2287352
• NM_198834.3:c.2164-214A>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.2164-214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,052 control chromosomes in the GnomAD database, including 19,653 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 0.48 (19653 hom., cov: 32)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531
• Publications: 4 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACA	NM_198834.3	c.2164-214A>G		intron_variant	Intron 17 of 55	ENST00000616317.5	NP_942131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACA	ENST00000616317.5	c.2164-214A>G		intron_variant	Intron 17 of 55	1	NM_198834.3	ENSP00000483300.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73162 AN: 151934 Hom.: 19597 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.482 AC: 73280 AN: 152052 Hom.: 19653 Cov.: 32 AF XY: 0.490 AC XY: 36425 AN XY: 74326

African (AFR) AF: 0.681 AC: 28230 AN: 41446

American (AMR) AF: 0.568 AC: 8684 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3464

East Asian (EAS) AF: 0.751 AC: 3887 AN: 5178

South Asian (SAS) AF: 0.605 AC: 2917 AN: 4822

European-Finnish (FIN) AF: 0.421 AC: 4449 AN: 10564

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22892 AN: 67978

Other (OTH) AF: 0.457 AC: 964 AN: 2110

Alfa AF: 0.368 Hom.: 4974

Bravo AF: 0.500

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.9
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs2287352; hg19: chr17-35605294;