rs6606697

Positions:

• chr12-109173915-A-G
• chr12-109173915-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACACB	NM_001093.4	c.1118-217A>G		intron_variant		ENST00000338432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACACB	ENST00000338432.12	c.1118-217A>G		intron_variant		1	NM_001093.4	P1
ACACB	ENST00000377848.7	c.1118-217A>G		intron_variant		1		P1
ACACB	ENST00000377854.9	c.-2885-217A>G		intron_variant		5

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

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.523

Alfa AF: 0.569 Hom.: 12613

Bravo AF: 0.460

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.024
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs6606697; hg19: chr12-109611720;