rs6497327

Variant names:

• chr16-8697027-C-T
• rs6497327
• NM_020686.6:c.-42+22316C>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.-42+22316C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,930 control chromosomes in the GnomAD database, including 18,802 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 0.49 (18802 hom., cov: 32)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 3 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 Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• 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 (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020686.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	NM_020686.6	MANE Select	c.-42+22316C>T		intron	N/A	NP_065737.2
	ABAT	NM_001386615.1		c.-42+22316C>T		intron	N/A	NP_001373544.1
	ABAT	NM_001386602.1		c.-143+22316C>T		intron	N/A	NP_001373531.1	X5D8S1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	ENST00000268251.13	TSL:1 MANE Select	c.-42+22316C>T		intron	N/A	ENSP00000268251.8	P80404
	ABAT	ENST00000909342.1		c.-143+22316C>T		intron	N/A	ENSP00000579401.1
	ABAT	ENST00000909343.1		c.-153-2290C>T		intron	N/A	ENSP00000579402.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73943 AN: 151808 Hom.: 18786 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.487 AC: 74004 AN: 151930 Hom.: 18802 Cov.: 32 AF XY: 0.492 AC XY: 36513 AN XY: 74222

African (AFR) AF: 0.327 AC: 13548 AN: 41430

American (AMR) AF: 0.559 AC: 8520 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1952 AN: 3468

East Asian (EAS) AF: 0.795 AC: 4112 AN: 5174

South Asian (SAS) AF: 0.602 AC: 2903 AN: 4820

European-Finnish (FIN) AF: 0.526 AC: 5522 AN: 10506

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35771 AN: 67970

Other (OTH) AF: 0.504 AC: 1060 AN: 2104

Alfa AF: 0.524 Hom.: 35733

Bravo AF: 0.486

Asia WGS AF: 0.673 AC: 2337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.98
DANN	Benign	0.77
PhyloP100		-1.4
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: rs6497327; hg19: chr16-8790884;