16-8774783-C-T

Variant names:

• chr16-8774783-C-T
• rs1641021
• NM_020686.6:c.955-107C>T

Variant summary

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

The NM_020686.6(ABAT):​c.955-107C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,367,610 control chromosomes in the GnomAD database, including 114,081 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 0.33 (9868 hom., cov: 32)
  • Exomes 𝑓: 0.41 (104213 hom.)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 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.955-107C>T		intron	N/A	NP_065737.2
	ABAT	NM_001386615.1		c.1051-107C>T		intron	N/A	NP_001373544.1
	ABAT	NM_001386616.1		c.955-107C>T		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.955-107C>T		intron	N/A	ENSP00000268251.8
	ABAT	ENST00000569156.5	TSL:1	c.955-107C>T		intron	N/A	ENSP00000454963.1
	ABAT	ENST00000566590.5	TSL:1	n.*695-107C>T		intron	N/A	ENSP00000455198.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50465 AN: 151934 Hom.: 9875 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.409 AC: 497442 AN: 1215556 Hom.: 104213 AF XY: 0.410 AC XY: 252238 AN XY: 615072

African (AFR) AF: 0.102 AC: 2946 AN: 28946

American (AMR) AF: 0.327 AC: 13771 AN: 42126

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 8732 AN: 24058

East Asian (EAS) AF: 0.385 AC: 14748 AN: 38354

South Asian (SAS) AF: 0.391 AC: 30979 AN: 79244

European-Finnish (FIN) AF: 0.484 AC: 21534 AN: 44488

Middle Eastern (MID) AF: 0.354 AC: 1281 AN: 3622

European-Non Finnish (NFE) AF: 0.425 AC: 383592 AN: 902606

Other (OTH) AF: 0.381 AC: 19859 AN: 52112

GnomAD4 genome AF: 0.332 AC: 50457 AN: 152054 Hom.: 9868 Cov.: 32 AF XY: 0.337 AC XY: 25049 AN XY: 74278

African (AFR) AF: 0.120 AC: 4979 AN: 41496

American (AMR) AF: 0.313 AC: 4789 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1247 AN: 3468

East Asian (EAS) AF: 0.400 AC: 2065 AN: 5166

South Asian (SAS) AF: 0.386 AC: 1857 AN: 4814

European-Finnish (FIN) AF: 0.514 AC: 5423 AN: 10542

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28976 AN: 67968

Other (OTH) AF: 0.336 AC: 708 AN: 2110

Alfa AF: 0.397 Hom.: 53183

Bravo AF: 0.309

Asia WGS AF: 0.348 AC: 1212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.49
PhyloP100		-0.32
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: rs1641021; hg19: chr16-8868640; COSMIC: COSV51630088;