chr12-109173915-A-G

Variant names:

• chr12-109173915-A-G
• rs6606697
• NM_001093.4:c.1118-217A>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.1118-217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,138 control chromosomes in the GnomAD database, including 19,531 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 0.48 (19531 hom., cov: 33)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001093.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	NM_001093.4	MANE Select	c.1118-217A>G		intron	N/A	NP_001084.3
	ACACB	NM_001412734.1		c.1118-217A>G		intron	N/A	NP_001399663.1
	ACACB	NM_001412735.1		c.1118-217A>G		intron	N/A	NP_001399664.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	ENST00000338432.12	TSL:1 MANE Select	c.1118-217A>G		intron	N/A	ENSP00000341044.7
	ACACB	ENST00000377848.7	TSL:1	c.1118-217A>G		intron	N/A	ENSP00000367079.3
	ACACB	ENST00000377854.9	TSL:5	c.-2885-217A>G		intron	N/A	ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73301 AN: 152020 Hom.: 19541 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.482 AC: 73289 AN: 152138 Hom.: 19531 Cov.: 33 AF XY: 0.479 AC XY: 35606 AN XY: 74354

African (AFR) AF: 0.273 AC: 11335 AN: 41506

American (AMR) AF: 0.411 AC: 6277 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2205 AN: 3470

East Asian (EAS) AF: 0.271 AC: 1405 AN: 5178

South Asian (SAS) AF: 0.460 AC: 2215 AN: 4816

European-Finnish (FIN) AF: 0.598 AC: 6316 AN: 10566

Middle Eastern (MID) AF: 0.710 AC: 206 AN: 290

European-Non Finnish (NFE) AF: 0.612 AC: 41587 AN: 67994

Other (OTH) AF: 0.523 AC: 1107 AN: 2116

Alfa AF: 0.569 Hom.: 14026

Bravo AF: 0.460

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.024
DANN	Benign	0.38
PhyloP100		-1.9
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: rs6606697; hg19: chr12-109611720; COSMIC: COSV108162440; COSMIC: COSV108162440;