rs9971877

Variant names:

• chr12-109231865-T-C
• rs9971877
• NM_001093.4:c.4002-804T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-109231865-T-C
• chr12-109231865-T-G

Variant summary

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

The NM_001093.4(ACACB):​c.4002-804T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,048 control chromosomes in the GnomAD database, including 12,801 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 0.39 (12801 hom., cov: 32)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.4002-804T>C		intron_variant	Intron 28 of 52	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.4002-804T>C		intron_variant	Intron 28 of 52	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.4002-804T>C		intron_variant	Intron 27 of 51	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-1-804T>C		intron_variant	Intron 27 of 46	5		ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59643 AN: 151930 Hom.: 12764 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.393 AC: 59738 AN: 152048 Hom.: 12801 Cov.: 32 AF XY: 0.393 AC XY: 29240 AN XY: 74322

African (AFR) AF: 0.580 AC: 24067 AN: 41462

American (AMR) AF: 0.300 AC: 4582 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1697 AN: 5166

South Asian (SAS) AF: 0.344 AC: 1660 AN: 4820

European-Finnish (FIN) AF: 0.351 AC: 3713 AN: 10572

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22065 AN: 67956

Other (OTH) AF: 0.361 AC: 762 AN: 2112

Alfa AF: 0.369 Hom.: 4186

Bravo AF: 0.389

Asia WGS AF: 0.365 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.50
PhyloP100		-0.42
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: rs9971877; hg19: chr12-109669670; COSMIC: COSV58139179; COSMIC: COSV58139179;