Genetic Variant ABAT:c.-42+12454G>C (chr16-8687165-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 NM_020686.6(ABAT):c.-42+12454G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,970 control chromosomes in the GnomAD database, including 35,850 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 0.68 ( 35850 hom., cov: 31)

Consequence

ABAT
NM_020686.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.660

Publications

5 publications found

Variant links:

Genes affected

ABAT (HGNC:23): (4-aminobutyrate aminotransferase) 4-aminobutyrate aminotransferase (ABAT) is responsible for catabolism of gamma-aminobutyric acid (GABA), an important, mostly inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde. The active enzyme is a homodimer of 50-kD subunits complexed to pyridoxal-5-phosphate. The protein sequence is over 95% similar to the pig protein. GABA is estimated to be present in nearly one-third of human synapses. ABAT in liver and brain is controlled by 2 codominant alleles with a frequency in a Caucasian population of 0.56 and 0.44. The ABAT deficiency phenotype includes psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

ABAT Gene-Disease associations (from GenCC):

GABA aminotransaminase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Orphanet, G2P
genetic developmental and epileptic encephalopathy
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ABAT links:

Genome browser will be placed here

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=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6 link	c.-42+12454G>C		intron_variant	Intron 1 of 15	ENST00000268251.13	NP_065737.2	P80404X5D8S1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABAT	ENST00000268251.13 link	c.-42+12454G>C	intron_variant	Intron 1 of 15	1	NM_020686.6	ENSP00000268251.8	P80404
ABAT	ENST00000564714.5 link	c.-64+12454G>C	intron_variant	Intron 1 of 5	3		ENSP00000456392.1	H3BRT1
ABAT	ENST00000563992.1 link	n.95+12454G>C	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.685

AC:

103994

AN:

151852

Hom.:

35821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.650

Gnomad AMI

AF:

0.631

Gnomad AMR

AF:

0.657

Gnomad ASJ

AF:

0.711

Gnomad EAS

AF:

0.824

Gnomad SAS

AF:

0.731

Gnomad FIN

AF:

0.648

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.691

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.685

AC:

104071

AN:

151970

Hom.:

35850

Cov.:

AF XY:

0.683

AC XY:

50754

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.650

AC:

26947

AN:

41448

American (AMR)

AF:

0.656

AC:

10029

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.711

AC:

2467

AN:

3468

East Asian (EAS)

AF:

0.824

AC:

4237

AN:

5144

South Asian (SAS)

AF:

0.733

AC:

3531

AN:

4816

European-Finnish (FIN)

AF:

0.648

AC:

6841

AN:

10552

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.703

AC:

47756

AN:

67948

Other (OTH)

AF:

0.690

AC:

1458

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1670

3340

5009

6679

8349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.690

Hom.:

4487

Bravo

AF:

0.684

Asia WGS

AF:

0.756

AC:

2629

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.47

(source)

DANN

Benign

0.44

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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