rs2239608

Variant names:

• chr12-109208917-A-C
• rs2239608
• NM_001093.4:c.3061-248A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ACACB Gene-Disease associations (from GenCC):

• isolated cleft palate

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.3061-248A>C		intron_variant	Intron 20 of 52	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.3061-248A>C		intron_variant	Intron 20 of 52	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.3061-248A>C		intron_variant	Intron 19 of 51	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-942-248A>C		intron_variant	Intron 19 of 46	5		ENSP00000367085.6

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

African (AFR) AF: 0.465 AC: 19278 AN: 41428

American (AMR) AF: 0.279 AC: 4260 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 966 AN: 3466

East Asian (EAS) AF: 0.338 AC: 1748 AN: 5168

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4818

European-Finnish (FIN) AF: 0.307 AC: 3250 AN: 10594

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19871 AN: 67946

Other (OTH) AF: 0.324 AC: 685 AN: 2116

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
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2239608; hg19: chr12-109646722;