Variant chr2-170818186-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000817.3(GAD1):c.-63-343T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 219,122 control chromosomes in the GnomAD database, including 51,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 33037 hom., cov: 28)

Exomes 𝑓: 0.73 ( 18799 hom. )

Consequence

GAD1
NM_000817.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.297

Variant links:

Genes affected

GAD1 (HGNC:4092): (glutamate decarboxylase 1) This gene encodes one of several forms of glutamic acid decarboxylase, identified as a major autoantigen in insulin-dependent diabetes. The enzyme encoded is responsible for catalyzing the production of gamma-aminobutyric acid from L-glutamic acid. A pathogenic role for this enzyme has been identified in the human pancreas since it has been identified as an autoantigen and an autoreactive T cell target in insulin-dependent diabetes. This gene may also play a role in the stiff man syndrome. Deficiency in this enzyme has been shown to lead to pyridoxine dependency with seizures. Alternative splicing of this gene results in two products, the predominant 67-kD form and a less-frequent 25-kD form. [provided by RefSeq, Jul 2008]

GAD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-170818186-T-C is Benign according to our data. Variant chr2-170818186-T-C is described in ClinVar as [Benign]. Clinvar id is 1233523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAD1	NM_000817.3 linkuse as main transcript	c.-63-343T>C		intron_variant		ENST00000358196.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAD1	ENST00000358196.8 linkuse as main transcript	c.-63-343T>C		intron_variant		1	NM_000817.3	P1	Q99259-1

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96435

AN:

151080

Hom.:

33025

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.688

Gnomad AMR

AF:

0.727

Gnomad ASJ

AF:

0.673

Gnomad EAS

AF:

0.716

Gnomad SAS

AF:

0.767

Gnomad FIN

AF:

0.741

Gnomad MID

AF:

0.583

Gnomad NFE

AF:

0.756

Gnomad OTH

AF:

0.676

GnomAD4 exome

AF:

0.728

AC:

49457

AN:

67930

Hom.:

18799

Cov.:

AF XY:

0.732

AC XY:

26367

AN XY:

36030

show subpopulations

Gnomad4 AFR exome

AF:

0.313

Gnomad4 AMR exome

AF:

0.728

Gnomad4 ASJ exome

AF:

0.635

Gnomad4 EAS exome

AF:

0.695

Gnomad4 SAS exome

AF:

0.767

Gnomad4 FIN exome

AF:

0.725

Gnomad4 NFE exome

AF:

0.751

Gnomad4 OTH exome

AF:

0.701

GnomAD4 genome

AF:

0.638

AC:

96471

AN:

151192

Hom.:

33037

Cov.:

AF XY:

0.642

AC XY:

47405

AN XY:

73824

show subpopulations

Gnomad4 AFR

AF:

0.354

Gnomad4 AMR

AF:

0.727

Gnomad4 ASJ

AF:

0.673

Gnomad4 EAS

AF:

0.716

Gnomad4 SAS

AF:

0.769

Gnomad4 FIN

AF:

0.741

Gnomad4 NFE

AF:

0.756

Gnomad4 OTH

AF:

0.676

Alfa

AF:

0.679

Hom.:

4583

Bravo

AF:

0.621

Asia WGS

AF:

0.737

AC:

2553

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

9.3

DANN

Benign

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over