chr2-170826230-C-T

Position:

• chr2-170826230-C-T

Variant summary

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

The NM_000817.3(GAD1):​c.146-3245C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,866 control chromosomes in the GnomAD database, including 10,765 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 0.36 (10765 hom., cov: 31)
• Consequence: GAD1 NM_000817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAD1	NM_000817.3	c.146-3245C>T		intron_variant		ENST00000358196.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAD1	ENST00000358196.8	c.146-3245C>T		intron_variant		1	NM_000817.3	P1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55294 AN: 151748 Hom.: 10768 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.364 AC: 55298 AN: 151866 Hom.: 10765 Cov.: 31 AF XY: 0.362 AC XY: 26858 AN XY: 74182

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.392

Alfa AF: 0.429 Hom.: 28829

Bravo AF: 0.358

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.68

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: rs3828275; hg19: chr2-171682740;