17-37185324-C-T

Variant names:

• chr17-37185324-C-T
• rs4794750
• NM_198834.3:c.4776+2953G>A

Variant summary

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

The NM_198834.3(ACACA):​c.4776+2953G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,298 control chromosomes in the GnomAD database, including 6,307 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 0.27 (6307 hom., cov: 30)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACA	NM_198834.3	c.4776+2953G>A		intron_variant	Intron 39 of 55	ENST00000616317.5	NP_942131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACA	ENST00000616317.5	c.4776+2953G>A		intron_variant	Intron 39 of 55	1	NM_198834.3	ENSP00000483300.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41229 AN: 151192 Hom.: 6290 Cov.: 30

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.273 AC: 41289 AN: 151298 Hom.: 6307 Cov.: 30 AF XY: 0.274 AC XY: 20217 AN XY: 73912

African (AFR) AF: 0.385 AC: 15861 AN: 41170

American (AMR) AF: 0.367 AC: 5579 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 390 AN: 3466

East Asian (EAS) AF: 0.306 AC: 1574 AN: 5140

South Asian (SAS) AF: 0.259 AC: 1242 AN: 4796

European-Finnish (FIN) AF: 0.229 AC: 2382 AN: 10394

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13570 AN: 67828

Other (OTH) AF: 0.249 AC: 523 AN: 2100

Alfa AF: 0.250 Hom.: 595

Bravo AF: 0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.9
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Other links and lift over

dbSNP: rs4794750; hg19: chr17-35542265;