chr16-8760130-T-C

Variant names:

• chr16-8760130-T-C
• rs8046201
• NM_020686.6:c.366+2324T>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.366+2324T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,148 control chromosomes in the GnomAD database, including 44,005 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 0.76 (43985 hom., cov: 32)
  • Exomes 𝑓: 0.87 (20 hom.)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 5 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, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Orphanet, G2P
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	NM_020686.6	MANE Select	c.366+2324T>C		intron	N/A	NP_065737.2
	ABAT	NM_001386615.1		c.462+2324T>C		intron	N/A	NP_001373544.1
	ABAT	NM_001386616.1		c.366+2324T>C		intron	N/A	NP_001373545.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	ENST00000268251.13	TSL:1 MANE Select	c.366+2324T>C		intron	N/A	ENSP00000268251.8
	ABAT	ENST00000569156.5	TSL:1	c.366+2324T>C		intron	N/A	ENSP00000454963.1
	ABAT	ENST00000566590.5	TSL:1	n.*106+2324T>C		intron	N/A	ENSP00000455198.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115438 AN: 151978 Hom.: 43958 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.740

GnomAD4 exome AF: 0.865 AC: 45 AN: 52 Hom.: 20 Cov.: 0 AF XY: 0.800 AC XY: 24 AN XY: 30

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.893 AC: 25 AN: 28

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 9 AN: 12

Other (OTH) AF: 0.900 AC: 9 AN: 10

GnomAD4 genome AF: 0.759 AC: 115513 AN: 152096 Hom.: 43985 Cov.: 32 AF XY: 0.758 AC XY: 56335 AN XY: 74346

African (AFR) AF: 0.711 AC: 29498 AN: 41472

American (AMR) AF: 0.796 AC: 12153 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2560 AN: 3470

East Asian (EAS) AF: 0.821 AC: 4244 AN: 5170

South Asian (SAS) AF: 0.690 AC: 3329 AN: 4824

European-Finnish (FIN) AF: 0.799 AC: 8452 AN: 10574

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52855 AN: 68006

Other (OTH) AF: 0.742 AC: 1569 AN: 2114

Alfa AF: 0.771 Hom.: 193168

Bravo AF: 0.757

Asia WGS AF: 0.780 AC: 2712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-0.16
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: rs8046201; hg19: chr16-8853987;