rs2268387

Positions:

• chr12-109205890-A-G
• chr12-109205890-A-T

Variant summary

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

The NM_001093.4(ACACB):​c.2914-820A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,044 control chromosomes in the GnomAD database, including 10,650 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 (10650 hom., cov: 31)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACACB	NM_001093.4	c.2914-820A>G		intron_variant		ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.2914-820A>G		intron_variant		1	NM_001093.4	ENSP00000341044	P1
ACACB	ENST00000377848.7	c.2914-820A>G		intron_variant		1		ENSP00000367079	P1
ACACB	ENST00000377854.9	c.-1089-820A>G		intron_variant		5		ENSP00000367085

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51545 AN: 151924 Hom.: 10654 Cov.: 31

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.339 AC: 51542 AN: 152044 Hom.: 10650 Cov.: 31 AF XY: 0.342 AC XY: 25441 AN XY: 74288

Gnomad4 AFR AF: 0.0970

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.387

Alfa AF: 0.421 Hom.: 18101

Bravo AF: 0.330

Asia WGS AF: 0.313 AC: 1087 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	0.72
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2268387; hg19: chr12-109643695;