12-109191652-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001093.4(ACACB):​c.2184C>T​(p.Gly728Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,613,776 control chromosomes in the GnomAD database, including 213,475 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 0.45 ( 16637 hom., cov: 32)
Exomes 𝑓: 0.51 ( 196838 hom. )

Consequence

ACACB
NM_001093.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP7
Synonymous conserved (PhyloP=-2.31 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACACBNM_001093.4 linkc.2184C>T p.Gly728Gly synonymous_variant Exon 14 of 53 ENST00000338432.12 NP_001084.3 O00763-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACACBENST00000338432.12 linkc.2184C>T p.Gly728Gly synonymous_variant Exon 14 of 53 1 NM_001093.4 ENSP00000341044.7 O00763-1
ACACBENST00000377848.7 linkc.2184C>T p.Gly728Gly synonymous_variant Exon 13 of 52 1 ENSP00000367079.3 O00763-1
ACACBENST00000377854 linkc.-1819C>T 5_prime_UTR_variant Exon 13 of 47 5 ENSP00000367085.6 F8W8T8
ACACBENST00000544651.1 linkn.175C>T non_coding_transcript_exon_variant Exon 1 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.449
AC:
68266
AN:
151904
Hom.:
16640
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.258
Gnomad AMI
AF:
0.701
Gnomad AMR
AF:
0.519
Gnomad ASJ
AF:
0.572
Gnomad EAS
AF:
0.264
Gnomad SAS
AF:
0.433
Gnomad FIN
AF:
0.524
Gnomad MID
AF:
0.674
Gnomad NFE
AF:
0.541
Gnomad OTH
AF:
0.503
GnomAD3 exomes
AF:
0.493
AC:
123965
AN:
251404
Hom.:
31947
AF XY:
0.498
AC XY:
67671
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.256
Gnomad AMR exome
AF:
0.545
Gnomad ASJ exome
AF:
0.573
Gnomad EAS exome
AF:
0.272
Gnomad SAS exome
AF:
0.447
Gnomad FIN exome
AF:
0.521
Gnomad NFE exome
AF:
0.545
Gnomad OTH exome
AF:
0.535
GnomAD4 exome
AF:
0.515
AC:
752291
AN:
1461754
Hom.:
196838
Cov.:
54
AF XY:
0.515
AC XY:
374210
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.248
Gnomad4 AMR exome
AF:
0.549
Gnomad4 ASJ exome
AF:
0.567
Gnomad4 EAS exome
AF:
0.256
Gnomad4 SAS exome
AF:
0.451
Gnomad4 FIN exome
AF:
0.521
Gnomad4 NFE exome
AF:
0.534
Gnomad4 OTH exome
AF:
0.502
GnomAD4 genome
AF:
0.449
AC:
68275
AN:
152022
Hom.:
16637
Cov.:
32
AF XY:
0.449
AC XY:
33328
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.258
Gnomad4 AMR
AF:
0.519
Gnomad4 ASJ
AF:
0.572
Gnomad4 EAS
AF:
0.265
Gnomad4 SAS
AF:
0.432
Gnomad4 FIN
AF:
0.524
Gnomad4 NFE
AF:
0.541
Gnomad4 OTH
AF:
0.500
Alfa
AF:
0.523
Hom.:
41922
Bravo
AF:
0.442
Asia WGS
AF:
0.370
AC:
1284
AN:
3476
EpiCase
AF:
0.562
EpiControl
AF:
0.559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
0.15
DANN
Benign
0.72

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7135947; hg19: chr12-109629457; COSMIC: COSV58130613; API