NM_001093.4:c.2144+65_2144+72dupTTCCTTCC

Variant names:

• chr12-109188171-C-CTCCTTCCT
• rs373209583
• NM_001093.4:c.2144+65_2144+72dupTTCCTTCC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001093.4(ACACB):​c.2144+65_2144+72dupTTCCTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (20 hom., cov: 0)
  • Exomes 𝑓: 0.0046 (85 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.839
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 12-109188171-C-CTCCTTCCT is Benign according to our data. Variant chr12-109188171-C-CTCCTTCCT is described in ClinVar as Likely_benign. ClinVar VariationId is 2037572.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.2144+65_2144+72dupTTCCTTCC		intron_variant	Intron 13 of 52	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.2144+9_2144+10insTCCTTCCT		intron_variant	Intron 13 of 52	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.2144+9_2144+10insTCCTTCCT		intron_variant	Intron 12 of 51	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-1859+9_-1859+10insTCCTTCCT		intron_variant	Intron 12 of 46	5		ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 1468 AN: 105006 Hom.: 20 Cov.: 0

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.00185

Gnomad EAS AF: 0.0532

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.00862

Gnomad NFE AF: 0.00624

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00418 AC: 781 AN: 187034 AF XY: 0.00352

Gnomad AFR exome AF: 0.00502

Gnomad AMR exome AF: 0.00939

Gnomad ASJ exome AF: 0.000654

Gnomad EAS exome AF: 0.0189

Gnomad FIN exome AF: 0.00601

Gnomad NFE exome AF: 0.00120

Gnomad OTH exome AF: 0.00407

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00462 AC: 5789 AN: 1251774 Hom.: 85 Cov.: 0 AF XY: 0.00474 AC XY: 2927 AN XY: 617762

African (AFR) AF: 0.00789 AC: 220 AN: 27896

American (AMR) AF: 0.0138 AC: 495 AN: 35876

Ashkenazi Jewish (ASJ) AF: 0.00137 AC: 30 AN: 21920

East Asian (EAS) AF: 0.0432 AC: 1430 AN: 33126

South Asian (SAS) AF: 0.00658 AC: 470 AN: 71430

European-Finnish (FIN) AF: 0.0278 AC: 1256 AN: 45236

Middle Eastern (MID) AF: 0.00294 AC: 13 AN: 4420

European-Non Finnish (NFE) AF: 0.00167 AC: 1608 AN: 961300

Other (OTH) AF: 0.00528 AC: 267 AN: 50570

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0140 AC: 1467 AN: 105096 Hom.: 20 Cov.: 0 AF XY: 0.0156 AC XY: 775 AN XY: 49708

African (AFR) AF: 0.0178 AC: 496 AN: 27888

American (AMR) AF: 0.0203 AC: 205 AN: 10074

Ashkenazi Jewish (ASJ) AF: 0.00185 AC: 5 AN: 2698

East Asian (EAS) AF: 0.0525 AC: 170 AN: 3240

South Asian (SAS) AF: 0.0127 AC: 31 AN: 2432

European-Finnish (FIN) AF: 0.0349 AC: 229 AN: 6568

Middle Eastern (MID) AF: 0.00952 AC: 2 AN: 210

European-Non Finnish (NFE) AF: 0.00624 AC: 312 AN: 50010

Other (OTH) AF: 0.0128 AC: 17 AN: 1330

Alfa AF: 0.0103 Hom.: 759

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs373209583; hg19: chr12-109625976;