rs2313427

Variant names:

• chr16-8721143-G-A
• rs2313427
• NM_020686.6:c.-41-14556G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-8721143-G-A
• chr16-8721143-G-C

Variant summary

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

The NM_020686.6(ABAT):​c.-41-14556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,034 control chromosomes in the GnomAD database, including 3,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.18 (3523 hom., cov: 32)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 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.-41-14556G>A		intron	N/A	NP_065737.2
	ABAT	NM_001386615.1		c.-41-14556G>A		intron	N/A	NP_001373544.1
	ABAT	NM_001386616.1		c.-42+209G>A		intron	N/A	NP_001373545.1	H3BNQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	ENST00000268251.13	TSL:1 MANE Select	c.-41-14556G>A		intron	N/A	ENSP00000268251.8	P80404
	ABAT	ENST00000569156.5	TSL:1	c.-42+209G>A		intron	N/A	ENSP00000454963.1	H3BNQ7
	ABAT	ENST00000566590.5	TSL:1	n.-42+7278G>A		intron	N/A	ENSP00000455198.1	H3BP84

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27124 AN: 151916 Hom.: 3517 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.179 AC: 27153 AN: 152034 Hom.: 3523 Cov.: 32 AF XY: 0.183 AC XY: 13568 AN XY: 74304

African (AFR) AF: 0.296 AC: 12283 AN: 41430

American (AMR) AF: 0.161 AC: 2458 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2870 AN: 5164

South Asian (SAS) AF: 0.274 AC: 1318 AN: 4804

European-Finnish (FIN) AF: 0.0748 AC: 792 AN: 10588

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0906 AC: 6158 AN: 67990

Other (OTH) AF: 0.187 AC: 393 AN: 2102

Alfa AF: 0.126 Hom.: 3217

Bravo AF: 0.188

Asia WGS AF: 0.395 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.9
DANN	Benign	0.50
PhyloP100		-0.34
PromoterAI		-0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2313427; hg19: chr16-8815000;