rs16939972

Positions:

• chr12-109130992-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• 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/exons	MANE	UniProt
ACACB	NM_001093.4	c.-9-8405T>C		intron_variant		ENST00000338432.12
LOC105369974	XR_945332.3	n.201+650A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACACB	ENST00000338432.12	c.-9-8405T>C		intron_variant		1	NM_001093.4	P1

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

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.573

Alfa AF: 0.590 Hom.: 7438

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

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: rs16939972; hg19: chr12-109568797;