rs2284685

Variant names:

• chr12-109248977-G-C
• rs2284685
• NM_001093.4:c.5670-1007G>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.5670-1007G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,102 control chromosomes in the GnomAD database, including 9,403 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 0.34 (9403 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.5670-1007G>C		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.5670-1007G>C		intron_variant	Intron 40 of 52	1	NM_001093.4	ENSP00000341044.7

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51085 AN: 151984 Hom.: 9395 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.342

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.336 AC: 51116 AN: 152102 Hom.: 9403 Cov.: 33 AF XY: 0.339 AC XY: 25188 AN XY: 74334

African (AFR) AF: 0.197 AC: 8159 AN: 41504

American (AMR) AF: 0.364 AC: 5563 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1451 AN: 5176

South Asian (SAS) AF: 0.301 AC: 1451 AN: 4824

European-Finnish (FIN) AF: 0.473 AC: 4992 AN: 10554

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27222 AN: 67972

Other (OTH) AF: 0.345 AC: 727 AN: 2110

Alfa AF: 0.360 Hom.: 1302

Bravo AF: 0.323

Asia WGS AF: 0.295 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.76
PhyloP100		-0.37
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: rs2284685; hg19: chr12-109686782;