17-37111115-A-G

Position:

• chr17-37111115-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198834.3(ACACA):​c.6565+416T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,878 control chromosomes in the GnomAD database, including 24,461 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 0.54 (24461 hom., cov: 31)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACACA	NM_198834.3	c.6565+416T>C		intron_variant		ENST00000616317.5	NP_942131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACACA	ENST00000616317.5	c.6565+416T>C		intron_variant		1	NM_198834.3	ENSP00000483300.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82031 AN: 151760 Hom.: 24399 Cov.: 31

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.541 AC: 82157 AN: 151878 Hom.: 24461 Cov.: 31 AF XY: 0.549 AC XY: 40718 AN XY: 74194

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.507

Alfa AF: 0.425 Hom.: 3933

Bravo AF: 0.559

Asia WGS AF: 0.724 AC: 2515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs1266175; hg19: chr17-35468050;