16-8761816-C-T

Variant names:

• chr16-8761816-C-T
• rs1273398
• NM_020686.6:c.367-2253C>T

Variant summary

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

The NM_020686.6(ABAT):​c.367-2253C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,064 control chromosomes in the GnomAD database, including 1,621 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 0.13 (1621 hom., cov: 32)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6	c.367-2253C>T		intron_variant	Intron 6 of 15	ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.367-2253C>T		intron_variant	Intron 6 of 15	1	NM_020686.6	ENSP00000268251.8

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19140 AN: 151946 Hom.: 1618 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0828

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.126 AC: 19163 AN: 152064 Hom.: 1621 Cov.: 32 AF XY: 0.128 AC XY: 9507 AN XY: 74340

African (AFR) AF: 0.240 AC: 9966 AN: 41454

American (AMR) AF: 0.0839 AC: 1281 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 231 AN: 3470

East Asian (EAS) AF: 0.143 AC: 740 AN: 5178

South Asian (SAS) AF: 0.170 AC: 817 AN: 4818

European-Finnish (FIN) AF: 0.0828 AC: 875 AN: 10574

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0733 AC: 4986 AN: 67992

Other (OTH) AF: 0.106 AC: 223 AN: 2108

Alfa AF: 0.0918 Hom.: 1561

Bravo AF: 0.126

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.52
PhyloP100		0.18
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: rs1273398; hg19: chr16-8855673;