Genetic Variant ENSG00000256139:n.664G>C (chr12-109113428-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000755022.1(ENSG00000256139):n.664G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,146 control chromosomes in the GnomAD database, including 6,108 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 0.26 ( 6107 hom., cov: 33)

Exomes 𝑓: 0.38 ( 1 hom. )

Consequence

ENSG00000256139
ENST00000755022.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.440

Publications

12 publications found

Variant links:

Genes affected

ENSG00000256139 (HGNC:):

ENSG00000256139 links:

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 links:

UNG (HGNC:12572): (uracil DNA glycosylase) This gene encodes one of several uracil-DNA glycosylases. One important function of uracil-DNA glycosylases is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosylic bond and initiating the base-excision repair (BER) pathway. Uracil bases occur from cytosine deamination or misincorporation of dUMP residues. Alternative promoter usage and splicing of this gene leads to two different isoforms: the mitochondrial UNG1 and the nuclear UNG2. The UNG2 term was used as a previous symbol for the CCNO gene (GeneID 10309), which has been confused with this gene, in the literature and some databases. [provided by RefSeq, Nov 2010]

UNG Gene-Disease associations (from GenCC):

hyper-IgM syndrome type 5
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

UNG links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
ACACB	NM_001412734.1 link	c.-10+13G>C	intron_variant	Intron 2 of 53	NP_001399663.1
ACACB	NM_001412737.1 link	c.26+13G>C	intron_variant	Intron 2 of 52	NP_001399666.1
ACACB	XM_011538263.4 link	c.-10+13G>C	intron_variant	Intron 1 of 51	XP_011536565.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000256139	ENST00000755022.1 link	n.664G>C	non_coding_transcript_exon_variant	Exon 2 of 2
UNG	ENST00000699563.1 link	c.774+9817G>C	intron_variant	Intron 5 of 5		ENSP00000514437.1	A0A8V8TNE1
ENSG00000256139	ENST00000541704.2 link	n.576+13G>C	intron_variant	Intron 2 of 2	5
ENSG00000256139	ENST00000755021.1 link	n.485+13G>C	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40206

AN:

152020

Hom.:

6104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.262

GnomAD4 exome

AF:

0.375

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.265

AC:

40242

AN:

152138

Hom.:

6107

Cov.:

AF XY:

0.261

AC XY:

19431

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.425

AC:

17613

AN:

41488

American (AMR)

AF:

0.179

AC:

2744

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

597

AN:

3472

East Asian (EAS)

AF:

0.105

AC:

544

AN:

5178

South Asian (SAS)

AF:

0.220

AC:

1059

AN:

4824

European-Finnish (FIN)

AF:

0.223

AC:

2351

AN:

10564

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.214

AC:

14555

AN:

68002

Other (OTH)

AF:

0.261

AC:

551

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1432

2864

4296

5728

7160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.145

Hom.:

283

Bravo

AF:

0.264

Asia WGS

AF:

0.180

AC:

628

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.22

(source)

DANN

Benign

0.57

PhyloP100

-0.44

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over