rs6497327

Positions:

• chr16-8697027-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABAT	NM_020686.6	c.-42+22316C>T		intron_variant		ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.-42+22316C>T		intron_variant		1	NM_020686.6	ENSP00000268251	P1
ABAT	ENST00000564714.5	c.-64+22316C>T		intron_variant		3		ENSP00000456392
ABAT	ENST00000563992.1	n.95+22316C>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.504

Alfa AF: 0.529 Hom.: 28809

Bravo AF: 0.486

Asia WGS AF: 0.673 AC: 2337 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	0.98
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs6497327; hg19: chr16-8790884;