rs2053670

Variant names:

• chr17-37109761-T-C
• rs2053670
• NM_198834.3:c.6565+1770A>G

Variant summary

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

The NM_198834.3(ACACA):​c.6565+1770A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,068 control chromosomes in the GnomAD database, including 13,131 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 (13131 hom., cov: 32)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACA	NM_198834.3	MANE Select	c.6565+1770A>G		intron	N/A	NP_942131.1	Q13085-4
	ACACA	NM_198836.3		c.6454+1770A>G		intron	N/A	NP_942133.1	Q13085-1
	ACACA	NM_198839.3		c.6454+1770A>G		intron	N/A	NP_942136.1	Q13085-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACA	ENST00000616317.5	TSL:1 MANE Select	c.6565+1770A>G		intron	N/A	ENSP00000483300.1	Q13085-4
	ACACA	ENST00000614428.4	TSL:1	c.6454+1770A>G		intron	N/A	ENSP00000478547.1	Q13085-1
	ACACA	ENST00000619546.4	TSL:1	c.2410+1770A>G		intron	N/A	ENSP00000483969.1	Q59FY4

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52653 AN: 151950 Hom.: 13088 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.347 AC: 52767 AN: 152068 Hom.: 13131 Cov.: 32 AF XY: 0.347 AC XY: 25791 AN XY: 74340

African (AFR) AF: 0.695 AC: 28824 AN: 41446

American (AMR) AF: 0.406 AC: 6211 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.311 AC: 1608 AN: 5174

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4822

European-Finnish (FIN) AF: 0.181 AC: 1910 AN: 10576

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11568 AN: 67980

Other (OTH) AF: 0.310 AC: 653 AN: 2106

Alfa AF: 0.215 Hom.: 8141

Bravo AF: 0.381

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.70
PhyloP100		0.46
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: rs2053670; hg19: chr17-35466696;