chr12-109208917-A-C

Position:

• chr12-109208917-A-C

Variant summary

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

The NM_001093.4(ACACB):​c.3061-248A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,014 control chromosomes in the GnomAD database, including 9,388 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 0.34 (9388 hom., cov: 31)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.690

Genes affected

ACACB (HGNC:85): (acetyl-CoA carboxylase beta) 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. ACC-beta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine-palmitoyl-CoA transferase I, the rate-limiting step in fatty acid uptake and oxidation by mitochondria. ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. [provided by RefSeq, Oct 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACACB	NM_001093.4	c.3061-248A>C		intron_variant		ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.3061-248A>C		intron_variant		1	NM_001093.4	ENSP00000341044	P1
ACACB	ENST00000377848.7	c.3061-248A>C		intron_variant		1		ENSP00000367079	P1
ACACB	ENST00000377854.9	c.-942-248A>C		intron_variant		5		ENSP00000367085

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51695 AN: 151896 Hom.: 9359 Cov.: 31

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.341 AC: 51774 AN: 152014 Hom.: 9388 Cov.: 31 AF XY: 0.341 AC XY: 25342 AN XY: 74298

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.324

Alfa AF: 0.228 Hom.: 887

Bravo AF: 0.340

Asia WGS AF: 0.334 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.61
DANN	Benign	0.25

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: rs2239608; hg19: chr12-109646722;