rs10492215

Positions:

• chr12-109129540-T-C

Variant summary

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

The ENST00000338432.12(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 ENST00000338432.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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]

LOC105369974 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACACB	NM_001093.4	c.-9-9857T>C		intron_variant		ENST00000338432.12	NP_001084.3
LOC105369974	XR_945332.3	n.202-1945A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.-9-9857T>C		intron_variant		1	NM_001093.4	ENSP00000341044	P1

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

Gnomad4 AFR AF: 0.0732

Gnomad4 AMR AF: 0.0724

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.0387

Gnomad4 FIN AF: 0.0686

Gnomad4 NFE AF: 0.0227

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0382 Hom.: 38

Bravo AF: 0.0572

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.52
DANN	Benign	0.61

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: rs10492215; hg19: chr12-109567345;