rs12149040

Variant names:

• chr16-8715995-A-G
• rs12149040
• NM_020686.6:c.-41-19704A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020686.6(ABAT):​c.-41-19704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,152 control chromosomes in the GnomAD database, including 1,497 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 0.12 (1497 hom., cov: 32)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 2 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6	c.-41-19704A>G		intron_variant	Intron 1 of 15	ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.-41-19704A>G		intron_variant	Intron 1 of 15	1	NM_020686.6	ENSP00000268251.8

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17624 AN: 152034 Hom.: 1486 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.116 AC: 17671 AN: 152152 Hom.: 1497 Cov.: 32 AF XY: 0.113 AC XY: 8406 AN XY: 74402

African (AFR) AF: 0.235 AC: 9726 AN: 41474

American (AMR) AF: 0.107 AC: 1631 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3472

East Asian (EAS) AF: 0.111 AC: 572 AN: 5168

South Asian (SAS) AF: 0.102 AC: 494 AN: 4824

European-Finnish (FIN) AF: 0.0327 AC: 347 AN: 10612

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0615 AC: 4180 AN: 67998

Other (OTH) AF: 0.120 AC: 254 AN: 2116

Alfa AF: 0.0970 Hom.: 385

Bravo AF: 0.126

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.71
PhyloP100		-0.070
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12149040; hg19: chr16-8809852;