12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT-CTCCTTCCTTCCTTCCTTCCT

Position:

• chr12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT-CTCCTTCCTTCCTTCCTTCCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001093.4(ACACB):​c.2144+53_2144+72del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00379 in 1,357,006 control chromosomes in the GnomAD database, including 62 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (36 hom., cov: 0)
  • Exomes 𝑓: 0.0027 (26 hom.)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

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 -10 ACMG points.

• BP6: Variant 12-109188171-CTCCTTCCTTCCTTCCTTCCT-C is Benign according to our data. Variant chr12-109188171-CTCCTTCCTTCCTTCCTTCCT-C is described in ClinVar as [Benign]. Clinvar id is 771459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0171 (1796/105134) while in subpopulation AFR AF= 0.0468 (1307/27902). AF 95% confidence interval is 0.0447. There are 36 homozygotes in gnomad4. There are 886 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 36 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACACB	NM_001093.4	c.2144+53_2144+72del		intron_variant		ENST00000338432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACACB	ENST00000338432.12	c.2144+53_2144+72del		intron_variant		1	NM_001093.4	P1
ACACB	ENST00000377848.7	c.2144+53_2144+72del		intron_variant		1		P1
ACACB	ENST00000377854.9	c.-1859+53_-1859+72del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 1792 AN: 105044 Hom.: 36 Cov.: 0

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.00619

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.000741

Gnomad EAS AF: 0.00583

Gnomad SAS AF: 0.00247

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00382

Gnomad OTH AF: 0.0114

GnomAD4 exome AF: 0.00267 AC: 3345 AN: 1251872 Hom.: 26 AF XY: 0.00269 AC XY: 1663 AN XY: 617824

Gnomad4 AFR exome AF: 0.0264

Gnomad4 AMR exome AF: 0.00295

Gnomad4 ASJ exome AF: 0.000228

Gnomad4 EAS exome AF: 0.00639

Gnomad4 SAS exome AF: 0.000630

Gnomad4 FIN exome AF: 0.0128

Gnomad4 NFE exome AF: 0.00150

Gnomad4 OTH exome AF: 0.00423

GnomAD4 genome AF: 0.0171 AC: 1796 AN: 105134 Hom.: 36 Cov.: 0 AF XY: 0.0178 AC XY: 886 AN XY: 49734

Gnomad4 AFR AF: 0.0468

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.000741

Gnomad4 EAS AF: 0.00585

Gnomad4 SAS AF: 0.00247

Gnomad4 FIN AF: 0.0190

Gnomad4 NFE AF: 0.00382

Gnomad4 OTH AF: 0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 28, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs373209583; hg19: chr12-109625976;