chr12-109248977-G-C

Position:

• chr12-109248977-G-C

Variant summary

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

The NM_001093.4(ACACB):​c.5670-1007G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,102 control chromosomes in the GnomAD database, including 9,403 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 (9403 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACACB	NM_001093.4	c.5670-1007G>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.5670-1007G>C		intron_variant		1	NM_001093.4	ENSP00000341044	P1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51085 AN: 151984 Hom.: 9395 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.342

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.336 AC: 51116 AN: 152102 Hom.: 9403 Cov.: 33 AF XY: 0.339 AC XY: 25188 AN XY: 74334

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.345

Alfa AF: 0.360 Hom.: 1302

Bravo AF: 0.323

Asia WGS AF: 0.295 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.76

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: rs2284685; hg19: chr12-109686782;