12-109247740-A-T

Variant names:

• chr12-109247740-A-T
• rs2284689
• NM_001093.4:c.5669+37A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001093.4(ACACB):​c.5669+37A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 14 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.5669+37A>T		intron_variant	Intron 40 of 52	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.5669+37A>T		intron_variant	Intron 40 of 52	1	NM_001093.4	ENSP00000341044.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 245392 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.24e-7 AC: 1 AN: 1380626 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 690996

African (AFR) AF: 0.00 AC: 0 AN: 31680

American (AMR) AF: 0.00 AC: 0 AN: 44164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25562

East Asian (EAS) AF: 0.00 AC: 0 AN: 39254

South Asian (SAS) AF: 0.00 AC: 0 AN: 83614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5242

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1040422

Other (OTH) AF: 0.0000173 AC: 1 AN: 57798

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 36405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.50
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2284689; hg19: chr12-109685545;