rs1299926

Variant names:

• chr16-8777224-T-A
• rs1299926
• NM_020686.6:c.1269+734T>A

Your query was ambiguous. Multiple possible variants found:

• chr16-8777224-T-A
• chr16-8777224-T-C
• chr16-8777224-T-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.1269+734T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,010 control chromosomes in the GnomAD database, including 59,073 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 0.87 (59073 hom., cov: 30)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6	c.1269+734T>A		intron_variant	Intron 14 of 15	ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.1269+734T>A		intron_variant	Intron 14 of 15	1	NM_020686.6	ENSP00000268251.8

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132697 AN: 151892 Hom.: 59057 Cov.: 30

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.873 AC: 132762 AN: 152010 Hom.: 59073 Cov.: 30 AF XY: 0.877 AC XY: 65166 AN XY: 74286

African (AFR) AF: 0.688 AC: 28471 AN: 41386

American (AMR) AF: 0.904 AC: 13790 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.930 AC: 3226 AN: 3470

East Asian (EAS) AF: 0.985 AC: 5087 AN: 5162

South Asian (SAS) AF: 0.963 AC: 4633 AN: 4812

European-Finnish (FIN) AF: 0.975 AC: 10335 AN: 10600

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64287 AN: 68008

Other (OTH) AF: 0.870 AC: 1833 AN: 2106

Alfa AF: 0.904 Hom.: 7806

Bravo AF: 0.858

Asia WGS AF: 0.957 AC: 3328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		-0.41
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: rs1299926; hg19: chr16-8871081;