chr17-37248370-T-C

Position:

• chr17-37248370-T-C

Variant summary

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

The NM_198834.3(ACACA):​c.2164-214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,052 control chromosomes in the GnomAD database, including 19,653 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 0.48 (19653 hom., cov: 32)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACACA	NM_198834.3	c.2164-214A>G		intron_variant		ENST00000616317.5	NP_942131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACACA	ENST00000616317.5	c.2164-214A>G		intron_variant		1	NM_198834.3	ENSP00000483300

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73162 AN: 151934 Hom.: 19597 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.482 AC: 73280 AN: 152052 Hom.: 19653 Cov.: 32 AF XY: 0.490 AC XY: 36425 AN XY: 74326

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.457

Alfa AF: 0.381 Hom.: 3065

Bravo AF: 0.500

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.9

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2287352; hg19: chr17-35605294;