chr2-170815865-C-T

Position:

• chr2-170815865-C-T

Variant summary

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

The ENST00000454603.5(GAD1):​c.-64+2443C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 152,302 control chromosomes in the GnomAD database, including 235 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 0.021 (235 hom., cov: 33)
• Consequence: GAD1 ENST00000454603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975

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]

ENSG00000235934 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAD1	XM_011510922.1	c.-64+2443C>T		intron_variant			XP_011509224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAD1	ENST00000454603.5	c.-64+2443C>T		intron_variant		4		ENSP00000402366.1
ENSG00000235934	ENST00000663207.1	n.959G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3202 AN: 152184 Hom.: 236 Cov.: 33

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.0430

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00550

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0211 AC: 3211 AN: 152302 Hom.: 235 Cov.: 33 AF XY: 0.0229 AC XY: 1707 AN XY: 74462

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.0197

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.0430

Gnomad4 FIN AF: 0.00509

Gnomad4 NFE AF: 0.00550

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.00581 Hom.: 4

Bravo AF: 0.0230

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.4
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6755102; hg19: chr2-171672375;