rs2239607

Variant names:

• chr12-109209475-A-G
• rs2239607
• NM_001093.4:c.3249+122A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001093.4(ACACB):​c.3249+122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 983,532 control chromosomes in the GnomAD database, including 14,739 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 0.14 (1921 hom., cov: 31)
  • Exomes 𝑓: 0.17 (12818 hom.)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.3249+122A>G		intron_variant	Intron 21 of 52	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.3249+122A>G		intron_variant	Intron 21 of 52	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.3249+122A>G		intron_variant	Intron 20 of 51	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-754+122A>G		intron_variant	Intron 20 of 46	5		ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21750 AN: 151936 Hom.: 1920 Cov.: 31

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.167 AC: 139121 AN: 831478 Hom.: 12818 AF XY: 0.169 AC XY: 70301 AN XY: 414912

African (AFR) AF: 0.0450 AC: 900 AN: 19978

American (AMR) AF: 0.153 AC: 3220 AN: 21002

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 2306 AN: 16102

East Asian (EAS) AF: 0.279 AC: 9071 AN: 32532

South Asian (SAS) AF: 0.202 AC: 10784 AN: 53444

European-Finnish (FIN) AF: 0.220 AC: 8045 AN: 36514

Middle Eastern (MID) AF: 0.150 AC: 409 AN: 2730

European-Non Finnish (NFE) AF: 0.160 AC: 97976 AN: 610700

Other (OTH) AF: 0.167 AC: 6410 AN: 38476

GnomAD4 genome AF: 0.143 AC: 21748 AN: 152054 Hom.: 1921 Cov.: 31 AF XY: 0.149 AC XY: 11054 AN XY: 74338

African (AFR) AF: 0.0500 AC: 2074 AN: 41486

American (AMR) AF: 0.153 AC: 2342 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 505 AN: 3470

East Asian (EAS) AF: 0.278 AC: 1431 AN: 5140

South Asian (SAS) AF: 0.211 AC: 1015 AN: 4818

European-Finnish (FIN) AF: 0.219 AC: 2315 AN: 10586

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11520 AN: 67958

Other (OTH) AF: 0.152 AC: 322 AN: 2114

Alfa AF: 0.167 Hom.: 481

Bravo AF: 0.132

Asia WGS AF: 0.232 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.27
PhyloP100		-0.15
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: rs2239607; hg19: chr12-109647280;