rs2239607

Variant names:

• chr12-109209475-A-G
• rs2239607
• NM_001093.4:c.3249+122A>G

Variant summary

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

The NM_001093.4(ACACB):​c.3249+122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 983,532 control chromosomes in the GnomAD database, including 14,739 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 0.14 (1921 hom., cov: 31)
  • Exomes 𝑓: 0.17 (12818 hom.)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.3249+122A>G		intron_variant	Intron 21 of 52	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.3249+122A>G		intron_variant	Intron 21 of 52	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.3249+122A>G		intron_variant	Intron 20 of 51	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-754+122A>G		intron_variant	Intron 20 of 46	5		ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21750 AN: 151936 Hom.: 1920 Cov.: 31

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.167 AC: 139121 AN: 831478 Hom.: 12818 AF XY: 0.169 AC XY: 70301 AN XY: 414912

Gnomad4 AFR exome AF: 0.0450

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.143 AC: 21748 AN: 152054 Hom.: 1921 Cov.: 31 AF XY: 0.149 AC XY: 11054 AN XY: 74338

Gnomad4 AFR AF: 0.0500

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.152

Alfa AF: 0.167 Hom.: 481

Bravo AF: 0.132

Asia WGS AF: 0.232 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.27

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: rs2239607; hg19: chr12-109647280;