chr17-37132758-G-A

Variant names:

• chr17-37132758-G-A
• rs7208415
• NM_198834.3:c.5680-2540C>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.5680-2540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,072 control chromosomes in the GnomAD database, including 3,043 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 (3043 hom., cov: 32)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACA	NM_198834.3	c.5680-2540C>T		intron_variant	Intron 45 of 55	ENST00000616317.5	NP_942131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACA	ENST00000616317.5	c.5680-2540C>T		intron_variant	Intron 45 of 55	1	NM_198834.3	ENSP00000483300.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27144 AN: 151954 Hom.: 3045 Cov.: 32

Gnomad AFR AF: 0.0722

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.179 AC: 27154 AN: 152072 Hom.: 3043 Cov.: 32 AF XY: 0.187 AC XY: 13933 AN XY: 74324

African (AFR) AF: 0.0721 AC: 2991 AN: 41484

American (AMR) AF: 0.190 AC: 2899 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 512 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2351 AN: 5160

South Asian (SAS) AF: 0.377 AC: 1818 AN: 4824

European-Finnish (FIN) AF: 0.288 AC: 3040 AN: 10558

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13007 AN: 67974

Other (OTH) AF: 0.188 AC: 397 AN: 2110

Alfa AF: 0.187 Hom.: 11327

Bravo AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.28
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs7208415; hg19: chr17-35489683;