NM_198834.3:c.39-18032T>C

Variant names:

• chr17-37357882-A-G
• rs4795194
• NM_198834.3:c.39-18032T>C

Variant summary

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

The NM_198834.3(ACACA):​c.39-18032T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,154 control chromosomes in the GnomAD database, including 3,231 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 0.18 (3231 hom., cov: 32)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198834.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACA	NM_198834.3	MANE Select	c.39-18032T>C		intron	N/A	NP_942131.1
	ACACA	NM_198836.3		c.-74+1117T>C		intron	N/A	NP_942133.1
	ACACA	NM_198839.3		c.-204+7561T>C		intron	N/A	NP_942136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACA	ENST00000616317.5	TSL:1 MANE Select	c.39-18032T>C		intron	N/A	ENSP00000483300.1
	ACACA	ENST00000614428.4	TSL:1	c.-74+1117T>C		intron	N/A	ENSP00000478547.1
	ACACA	ENST00000616352.4	TSL:1	c.-204+7561T>C		intron	N/A	ENSP00000477912.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27396 AN: 152034 Hom.: 3236 Cov.: 32

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.180 AC: 27386 AN: 152154 Hom.: 3231 Cov.: 32 AF XY: 0.188 AC XY: 13953 AN XY: 74374

African (AFR) AF: 0.0491 AC: 2038 AN: 41538

American (AMR) AF: 0.182 AC: 2778 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 713 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2560 AN: 5156

South Asian (SAS) AF: 0.276 AC: 1333 AN: 4822

European-Finnish (FIN) AF: 0.322 AC: 3409 AN: 10592

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13972 AN: 67986

Other (OTH) AF: 0.182 AC: 385 AN: 2116

Alfa AF: 0.198 Hom.: 6212

Bravo AF: 0.166

Asia WGS AF: 0.323 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		0.68
Mutation Taster		=100/0	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: rs4795194; hg19: chr17-35714825;