rs10492215

Variant names:

• chr12-109129540-T-C
• rs10492215
• NM_001093.4:c.-9-9857T>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.-9-9857T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 152,262 control chromosomes in the GnomAD database, including 415 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 0.054 (415 hom., cov: 32)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 2 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)

ENSG00000298358 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	NM_001093.4	MANE Select	c.-9-9857T>C		intron	N/A	NP_001084.3
	ACACB	NM_001412734.1		c.-9-9857T>C		intron	N/A	NP_001399663.1
	ACACB	NM_001412737.1		c.26+16125T>C		intron	N/A	NP_001399666.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	ENST00000338432.12	TSL:1 MANE Select	c.-9-9857T>C		intron	N/A	ENSP00000341044.7
	ENSG00000298358	ENST00000755079.1		n.224-1945A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8179 AN: 152144 Hom.: 410 Cov.: 32

Gnomad AFR AF: 0.0728

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.0531

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

GnomAD4 genome AF: 0.0539 AC: 8209 AN: 152262 Hom.: 415 Cov.: 32 AF XY: 0.0569 AC XY: 4237 AN XY: 74446

African (AFR) AF: 0.0732 AC: 3043 AN: 41544

American (AMR) AF: 0.0724 AC: 1107 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3472

East Asian (EAS) AF: 0.255 AC: 1322 AN: 5176

South Asian (SAS) AF: 0.0387 AC: 187 AN: 4830

European-Finnish (FIN) AF: 0.0686 AC: 728 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0227 AC: 1545 AN: 68018

Other (OTH) AF: 0.0539 AC: 114 AN: 2114

Alfa AF: 0.0423 Hom.: 143

Bravo AF: 0.0572

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.52
DANN	Benign	0.61
PhyloP100		-1.0
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: rs10492215; hg19: chr12-109567345;