rs16939972

Variant names:

• chr12-109130992-T-C
• rs16939972
• NM_001093.4:c.-9-8405T>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.-9-8405T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,924 control chromosomes in the GnomAD database, including 23,635 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 0.54 (23635 hom., cov: 31)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.-9-8405T>C		intron_variant	Intron 1 of 52	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.-9-8405T>C		intron_variant	Intron 1 of 52	1	NM_001093.4	ENSP00000341044.7
ENSG00000298358	ENST00000755079.1	n.223+650A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81415 AN: 151806 Hom.: 23641 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.536 AC: 81407 AN: 151924 Hom.: 23635 Cov.: 31 AF XY: 0.532 AC XY: 39501 AN XY: 74264

African (AFR) AF: 0.323 AC: 13378 AN: 41424

American (AMR) AF: 0.471 AC: 7186 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2229 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1631 AN: 5150

South Asian (SAS) AF: 0.517 AC: 2489 AN: 4812

European-Finnish (FIN) AF: 0.634 AC: 6688 AN: 10544

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45677 AN: 67946

Other (OTH) AF: 0.573 AC: 1210 AN: 2110

Alfa AF: 0.600 Hom.: 11643

Bravo AF: 0.516

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.74
PhyloP100		-0.048
PromoterAI		-0.011	Neutral
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: rs16939972; hg19: chr12-109568797;