rs741402

Variant names:

• chr12-109146550-A-G
• rs741402
• NM_001093.4:c.653+6492A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-109146550-A-G
• chr12-109146550-A-T

Variant summary

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

The NM_001093.4(ACACB):​c.653+6492A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,972 control chromosomes in the GnomAD database, including 17,685 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 0.46 (17685 hom., cov: 32)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.653+6492A>G		intron_variant	Intron 2 of 52	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.653+6492A>G		intron_variant	Intron 2 of 52	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.653+6492A>G		intron_variant	Intron 1 of 51	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-3350+6492A>G		intron_variant	Intron 1 of 46	5		ENSP00000367085.6
ACACB	ENST00000546328.1	n.80+6492A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69904 AN: 151854 Hom.: 17691 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.460 AC: 69893 AN: 151972 Hom.: 17685 Cov.: 32 AF XY: 0.454 AC XY: 33736 AN XY: 74270

African (AFR) AF: 0.266 AC: 11032 AN: 41444

American (AMR) AF: 0.407 AC: 6215 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2154 AN: 3470

East Asian (EAS) AF: 0.254 AC: 1313 AN: 5174

South Asian (SAS) AF: 0.446 AC: 2142 AN: 4798

European-Finnish (FIN) AF: 0.519 AC: 5471 AN: 10542

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39677 AN: 67960

Other (OTH) AF: 0.501 AC: 1057 AN: 2108

Alfa AF: 0.556 Hom.: 14054

Bravo AF: 0.445

Asia WGS AF: 0.351 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.64
PhyloP100		0.23
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: rs741402; hg19: chr12-109584355; COSMIC: COSV108162439;