NM_001093.4:c.19C>T

Variant names:

• chr12-109139424-C-T
• rs79484712
• NM_001093.4:c.19C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001093.4(ACACB):​c.19C>T​(p.Leu7Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,613,358 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0086 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (17 hom.)
• Consequence: ACACB NM_001093.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00900
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 12-109139424-C-T is Benign according to our data. Variant chr12-109139424-C-T is described in ClinVar as Benign. ClinVar VariationId is 768579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.009 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0086 (1310/152296) while in subpopulation AFR AF = 0.0296 (1231/41556). AF 95% confidence interval is 0.0282. There are 19 homozygotes in GnomAd4. There are 608 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 Unknown gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	NM_001093.4	MANE Select	c.19C>T	p.Leu7Leu	synonymous	Exon 2 of 53	NP_001084.3	O00763-1
	ACACB	NM_001412734.1		c.19C>T	p.Leu7Leu	synonymous	Exon 3 of 54	NP_001399663.1	O00763-1
	ACACB	NM_001412735.1		c.19C>T	p.Leu7Leu	synonymous	Exon 2 of 53	NP_001399664.1	O00763-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	ENST00000338432.12	TSL:1 MANE Select	c.19C>T	p.Leu7Leu	synonymous	Exon 2 of 53	ENSP00000341044.7	O00763-1
	ACACB	ENST00000377848.7	TSL:1	c.19C>T	p.Leu7Leu	synonymous	Exon 1 of 52	ENSP00000367079.3	O00763-1
	ACACB	ENST00000377854.9	TSL:5	c.-3984C>T		5_prime_UTR	Exon 1 of 47	ENSP00000367085.6	F8W8T8

Frequencies

GnomAD3 genomes AF: 0.00858 AC: 1305 AN: 152178 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00223 AC: 560 AN: 250772 AF XY: 0.00170

Gnomad AFR exome AF: 0.0293

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00108 AC: 1579 AN: 1461062 Hom.: 17 Cov.: 30 AF XY: 0.000952 AC XY: 692 AN XY: 726822

African (AFR) AF: 0.0324 AC: 1083 AN: 33420

American (AMR) AF: 0.00150 AC: 67 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5762

European-Non Finnish (NFE) AF: 0.000217 AC: 241 AN: 1111568

Other (OTH) AF: 0.00249 AC: 150 AN: 60342

GnomAD4 genome AF: 0.00860 AC: 1310 AN: 152296 Hom.: 19 Cov.: 32 AF XY: 0.00816 AC XY: 608 AN XY: 74482

African (AFR) AF: 0.0296 AC: 1231 AN: 41556

American (AMR) AF: 0.00248 AC: 38 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68024

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00359 Hom.: 7

Bravo AF: 0.00975

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ACACB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	3.2
DANN	Benign	0.71
PhyloP100		0.0090
PromoterAI		0.045	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79484712; hg19: chr12-109577229;