rs2878960

Variant names:

• chr12-109139930-C-T
• rs2878960
• NM_001093.4:c.525C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001093.4(ACACB):​c.525C>T​(p.Ser175Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,613,780 control chromosomes in the GnomAD database, including 319,608 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 0.52 (23075 hom., cov: 32)
  • Exomes 𝑓: 0.63 (296533 hom.)
• Consequence: ACACB NM_001093.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 25 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-2.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 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.525C>T	p.Ser175Ser	synonymous	Exon 2 of 53	NP_001084.3
	ACACB	NM_001412734.1		c.525C>T	p.Ser175Ser	synonymous	Exon 3 of 54	NP_001399663.1
	ACACB	NM_001412735.1		c.525C>T	p.Ser175Ser	synonymous	Exon 2 of 53	NP_001399664.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	ENST00000338432.12	TSL:1 MANE Select	c.525C>T	p.Ser175Ser	synonymous	Exon 2 of 53	ENSP00000341044.7
	ACACB	ENST00000377848.7	TSL:1	c.525C>T	p.Ser175Ser	synonymous	Exon 1 of 52	ENSP00000367079.3
	ACACB	ENST00000377854.9	TSL:5	c.-3478C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 47	ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79701 AN: 151966 Hom.: 23084 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.564

GnomAD2 exomes AF: 0.553 AC: 138337 AN: 250234 AF XY: 0.567

Gnomad AFR exome AF: 0.296

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.640

Gnomad EAS exome AF: 0.256

Gnomad FIN exome AF: 0.666

Gnomad NFE exome AF: 0.672

Gnomad OTH exome AF: 0.609

GnomAD4 exome AF: 0.628 AC: 917292 AN: 1461696 Hom.: 296533 Cov.: 77 AF XY: 0.627 AC XY: 456239 AN XY: 727156

African (AFR) AF: 0.290 AC: 9692 AN: 33470

American (AMR) AF: 0.384 AC: 17148 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 16671 AN: 26128

East Asian (EAS) AF: 0.228 AC: 9053 AN: 39698

South Asian (SAS) AF: 0.517 AC: 44568 AN: 86242

European-Finnish (FIN) AF: 0.661 AC: 35245 AN: 53356

Middle Eastern (MID) AF: 0.676 AC: 3897 AN: 5768

European-Non Finnish (NFE) AF: 0.669 AC: 744303 AN: 1111946

Other (OTH) AF: 0.608 AC: 36715 AN: 60390

GnomAD4 genome AF: 0.524 AC: 79686 AN: 152084 Hom.: 23075 Cov.: 32 AF XY: 0.520 AC XY: 38691 AN XY: 74352

African (AFR) AF: 0.296 AC: 12285 AN: 41484

American (AMR) AF: 0.462 AC: 7061 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2212 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1298 AN: 5158

South Asian (SAS) AF: 0.491 AC: 2363 AN: 4814

European-Finnish (FIN) AF: 0.660 AC: 6994 AN: 10594

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45443 AN: 67970

Other (OTH) AF: 0.560 AC: 1183 AN: 2114

Alfa AF: 0.611 Hom.: 88044

Bravo AF: 0.500

Asia WGS AF: 0.372 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.076
DANN	Benign	0.60
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs2878960; hg19: chr12-109577735; COSMIC: COSV58135326; COSMIC: COSV58135326;