chr17-37374913-C-G

Variant names:

• chr17-37374913-C-G
• rs11650168
• NM_198834.3:c.38+31349G>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.38+31349G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,864 control chromosomes in the GnomAD database, including 16,873 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 0.45 (16873 hom., cov: 31)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 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.38+31349G>C		intron	N/A	NP_942131.1
	ACACA	NM_198839.3		c.-747-5426G>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.38+31349G>C		intron	N/A	ENSP00000483300.1
	ACACA	ENST00000616352.4	TSL:1	c.-747-5426G>C		intron	N/A	ENSP00000477912.1
	ACACA	ENST00000615229.4	TSL:1	n.38+31349G>C		intron	N/A	ENSP00000482498.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68630 AN: 151748 Hom.: 16843 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.452 AC: 68702 AN: 151864 Hom.: 16873 Cov.: 31 AF XY: 0.457 AC XY: 33890 AN XY: 74190

African (AFR) AF: 0.617 AC: 25542 AN: 41410

American (AMR) AF: 0.345 AC: 5253 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1043 AN: 3468

East Asian (EAS) AF: 0.738 AC: 3794 AN: 5142

South Asian (SAS) AF: 0.441 AC: 2122 AN: 4814

European-Finnish (FIN) AF: 0.501 AC: 5293 AN: 10556

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24419 AN: 67940

Other (OTH) AF: 0.420 AC: 886 AN: 2108

Alfa AF: 0.414 Hom.: 1746

Bravo AF: 0.449

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.83
PhyloP100		-0.55

Splicing

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

Other links and lift over

dbSNP: rs11650168; hg19: chr17-35731855;