17-37103475-A-T

Variant names:

• chr17-37103475-A-T
• rs9330249
• NM_198834.3:c.6566-5491T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_198834.3(ACACA):​c.6566-5491T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,016 control chromosomes in the GnomAD database, including 13,068 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 0.35 (13068 hom., cov: 32)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACA	NM_198834.3	c.6566-5491T>A		intron_variant	Intron 52 of 55	ENST00000616317.5	NP_942131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACA	ENST00000616317.5	c.6566-5491T>A		intron_variant	Intron 52 of 55	1	NM_198834.3	ENSP00000483300.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52516 AN: 151898 Hom.: 13025 Cov.: 32

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.346 AC: 52630 AN: 152016 Hom.: 13068 Cov.: 32 AF XY: 0.346 AC XY: 25713 AN XY: 74304

African (AFR) AF: 0.694 AC: 28749 AN: 41434

American (AMR) AF: 0.406 AC: 6202 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3470

East Asian (EAS) AF: 0.308 AC: 1593 AN: 5172

South Asian (SAS) AF: 0.258 AC: 1238 AN: 4806

European-Finnish (FIN) AF: 0.180 AC: 1908 AN: 10598

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.170 AC: 11541 AN: 67968

Other (OTH) AF: 0.309 AC: 650 AN: 2104

Alfa AF: 0.271 Hom.: 1027

Bravo AF: 0.380

Asia WGS AF: 0.343 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.81
PhyloP100		2.7
Mutation Taster		=98/2	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: rs9330249; hg19: chr17-35460410;