rs2313427

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABAT	NM_020686.6	c.-41-14556G>A		intron_variant		ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.-41-14556G>A		intron_variant		1	NM_020686.6	ENSP00000268251	P1

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

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.0748

Gnomad4 NFE AF: 0.0906

Gnomad4 OTH AF: 0.187

Alfa AF: 0.115 Hom.: 1777

Bravo AF: 0.188

Asia WGS AF: 0.395 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.9
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs2313427; hg19: chr16-8815000;