rs9330248

Variant names:

• chr17-37087829-G-A
• rs9330248
• NM_198834.3:c.7029-390C>T

Variant summary

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

The NM_198834.3(ACACA):​c.7029-390C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,104 control chromosomes in the GnomAD database, including 5,623 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 0.24 (5623 hom., cov: 32)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACA	NM_198834.3	c.7029-390C>T		intron_variant	Intron 55 of 55	ENST00000616317.5	NP_942131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACA	ENST00000616317.5	c.7029-390C>T		intron_variant	Intron 55 of 55	1	NM_198834.3	ENSP00000483300.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37197 AN: 151986 Hom.: 5612 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.245 AC: 37249 AN: 152104 Hom.: 5623 Cov.: 32 AF XY: 0.246 AC XY: 18324 AN XY: 74366

African (AFR) AF: 0.396 AC: 16419 AN: 41472

American (AMR) AF: 0.351 AC: 5362 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 324 AN: 3470

East Asian (EAS) AF: 0.264 AC: 1369 AN: 5178

South Asian (SAS) AF: 0.216 AC: 1043 AN: 4820

European-Finnish (FIN) AF: 0.164 AC: 1740 AN: 10582

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

European-Non Finnish (NFE) AF: 0.152 AC: 10349 AN: 68000

Other (OTH) AF: 0.226 AC: 477 AN: 2108

Alfa AF: 0.182 Hom.: 1705

Bravo AF: 0.267

Asia WGS AF: 0.279 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.88
DANN	Benign	0.57
PhyloP100		-0.096
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9330248; hg19: chr17-35444764;