rs1641021

Positions:

• chr16-8774783-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.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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABAT	NM_020686.6	c.955-107C>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.955-107C>T		intron_variant		1	NM_020686.6	ENSP00000268251.8

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

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.484

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.381

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

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.336

Alfa AF: 0.412 Hom.: 26988

Bravo AF: 0.309

Asia WGS AF: 0.348 AC: 1212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.49

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: rs1641021; hg19: chr16-8868640; COSMIC: COSV51630088;