12-109266520-C-T

Variant names:

• chr12-109266520-C-T
• rs2075263
• NM_001093.4:c.*158C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001093.4(ACACB):​c.*158C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 905,104 control chromosomes in the GnomAD database, including 294,443 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 0.82 (51082 hom., cov: 32)
  • Exomes 𝑓: 0.80 (243361 hom.)
• Consequence: ACACB NM_001093.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 23 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001093.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	NM_001093.4	MANE Select	c.*158C>T		3_prime_UTR	Exon 53 of 53	NP_001084.3	O00763-1
	ACACB	NM_001412734.1		c.*158C>T		3_prime_UTR	Exon 54 of 54	NP_001399663.1	O00763-1
	ACACB	NM_001412735.1		c.*158C>T		3_prime_UTR	Exon 53 of 53	NP_001399664.1	O00763-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	ENST00000338432.12	TSL:1 MANE Select	c.*158C>T		3_prime_UTR	Exon 53 of 53	ENSP00000341044.7	O00763-1
	ACACB	ENST00000377848.7	TSL:1	c.*158C>T		3_prime_UTR	Exon 52 of 52	ENSP00000367079.3	O00763-1
	ACACB	ENST00000537279.1	TSL:2	n.1958C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124444 AN: 152052 Hom.: 51056 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.803 AC: 604528 AN: 752934 Hom.: 243361 Cov.: 10 AF XY: 0.800 AC XY: 298555 AN XY: 373410

African (AFR) AF: 0.828 AC: 13159 AN: 15892

American (AMR) AF: 0.878 AC: 8997 AN: 10250

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 11569 AN: 14002

East Asian (EAS) AF: 0.762 AC: 19656 AN: 25812

South Asian (SAS) AF: 0.675 AC: 24807 AN: 36736

European-Finnish (FIN) AF: 0.848 AC: 23419 AN: 27630

Middle Eastern (MID) AF: 0.797 AC: 2003 AN: 2514

European-Non Finnish (NFE) AF: 0.808 AC: 473297 AN: 585524

Other (OTH) AF: 0.799 AC: 27621 AN: 34574

GnomAD4 genome AF: 0.818 AC: 124520 AN: 152170 Hom.: 51082 Cov.: 32 AF XY: 0.819 AC XY: 60899 AN XY: 74398

African (AFR) AF: 0.826 AC: 34268 AN: 41480

American (AMR) AF: 0.856 AC: 13105 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2931 AN: 3472

East Asian (EAS) AF: 0.740 AC: 3824 AN: 5166

South Asian (SAS) AF: 0.660 AC: 3181 AN: 4822

European-Finnish (FIN) AF: 0.851 AC: 9028 AN: 10604

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55555 AN: 68010

Other (OTH) AF: 0.814 AC: 1715 AN: 2108

Alfa AF: 0.815 Hom.: 219837

Bravo AF: 0.822

Asia WGS AF: 0.723 AC: 2514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.53
PhyloP100		0.28
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: rs2075263; hg19: chr12-109704325;