rs2229416

Variant names:

• chr17-37252940-C-T
• rs2229416
• NM_198834.3:c.1923G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-37252940-C-T
• chr17-37252940-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_198834.3(ACACA):​c.1923G>A​(p.Gln641Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.145 in 1,614,036 control chromosomes in the GnomAD database, including 21,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1879 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19864 hom.)
• Consequence: ACACA NM_198834.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.09
• Publications: 23 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 17-37252940-C-T is Benign according to our data. Variant chr17-37252940-C-T is described in ClinVar as Benign. ClinVar VariationId is 559346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 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.1923G>A	p.Gln641Gln	synonymous	Exon 15 of 56	NP_942131.1	Q13085-4
	ACACA	NM_198836.3		c.1812G>A	p.Gln604Gln	synonymous	Exon 15 of 56	NP_942133.1	Q13085-1
	ACACA	NM_198839.3		c.1812G>A	p.Gln604Gln	synonymous	Exon 19 of 60	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.1923G>A	p.Gln641Gln	synonymous	Exon 15 of 56	ENSP00000483300.1	Q13085-4
	ACACA	ENST00000614428.4	TSL:1	c.1812G>A	p.Gln604Gln	synonymous	Exon 15 of 56	ENSP00000478547.1	Q13085-1
	ACACA	ENST00000613146.4	TSL:1	n.2008G>A		non_coding_transcript_exon	Exon 15 of 29

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19451 AN: 152078 Hom.: 1877 Cov.: 32

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.0419

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.135

GnomAD2 exomes AF: 0.181 AC: 45439 AN: 251476 AF XY: 0.189

Gnomad AFR exome AF: 0.0339

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.466

Gnomad FIN exome AF: 0.189

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.147 AC: 214602 AN: 1461840 Hom.: 19864 Cov.: 34 AF XY: 0.153 AC XY: 111011 AN XY: 727232

African (AFR) AF: 0.0322 AC: 1079 AN: 33480

American (AMR) AF: 0.145 AC: 6479 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3401 AN: 26136

East Asian (EAS) AF: 0.421 AC: 16698 AN: 39698

South Asian (SAS) AF: 0.332 AC: 28645 AN: 86256

European-Finnish (FIN) AF: 0.182 AC: 9705 AN: 53416

Middle Eastern (MID) AF: 0.197 AC: 1136 AN: 5768

European-Non Finnish (NFE) AF: 0.124 AC: 137475 AN: 1111968

Other (OTH) AF: 0.165 AC: 9984 AN: 60394

GnomAD4 genome AF: 0.128 AC: 19467 AN: 152196 Hom.: 1879 Cov.: 32 AF XY: 0.138 AC XY: 10233 AN XY: 74402

African (AFR) AF: 0.0392 AC: 1628 AN: 41546

American (AMR) AF: 0.154 AC: 2351 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3470

East Asian (EAS) AF: 0.445 AC: 2295 AN: 5156

South Asian (SAS) AF: 0.342 AC: 1647 AN: 4816

European-Finnish (FIN) AF: 0.191 AC: 2019 AN: 10584

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

European-Non Finnish (NFE) AF: 0.128 AC: 8684 AN: 68008

Other (OTH) AF: 0.138 AC: 292 AN: 2114

Alfa AF: 0.126 Hom.: 1486

Bravo AF: 0.117

Asia WGS AF: 0.353 AC: 1226 AN: 3478

EpiCase AF: 0.130

EpiControl AF: 0.130

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	ACACA-related disorder (1)
-	-	1	Acetyl-CoA: carboxylase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.5
DANN	Benign	0.72
PhyloP100		4.1
Mutation Taster		=97/3	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: rs2229416; hg19: chr17-35609866;