16-8712564-T-C

Position:

• chr16-8712564-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020686.6(ABAT):​c.-41-23135T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 151,970 control chromosomes in the GnomAD database, including 37,001 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 0.69 (37001 hom., cov: 31)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABAT	NM_020686.6	c.-41-23135T>C		intron_variant		ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.-41-23135T>C		intron_variant		1	NM_020686.6	ENSP00000268251	P1
ABAT	ENST00000564714.5	c.-63-10203T>C		intron_variant		3		ENSP00000456392
ABAT	ENST00000563992.1	n.96-23135T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104538 AN: 151852 Hom.: 36977 Cov.: 31

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.688 AC: 104602 AN: 151970 Hom.: 37001 Cov.: 31 AF XY: 0.688 AC XY: 51055 AN XY: 74260

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.721

Alfa AF: 0.749 Hom.: 41794

Bravo AF: 0.688

Asia WGS AF: 0.809 AC: 2808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.5
DANN	Benign	0.55

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: rs1273385; hg19: chr16-8806421; COSMIC: COSV51628444; COSMIC: COSV51628444;