rs769395

Variant names:

• chr2-170860293-G-A
• rs769395
• NM_000817.3:c.*411G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-170860293-G-A
• chr2-170860293-G-C
• chr2-170860293-G-T

Variant summary

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

The NM_000817.3(GAD1):​c.*411G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 185,014 control chromosomes in the GnomAD database, including 53,094 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 0.76 (43988 hom., cov: 32)
  • Exomes 𝑓: 0.73 (9106 hom.)
• Consequence: GAD1 NM_000817.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAD1	NM_000817.3	c.*411G>A		3_prime_UTR_variant	Exon 17 of 17	ENST00000358196.8	NP_000808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAD1	ENST00000358196.8	c.*411G>A		3_prime_UTR_variant	Exon 17 of 17	1	NM_000817.3	ENSP00000350928.3

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115381 AN: 151950 Hom.: 43952 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.773

GnomAD4 exome AF: 0.734 AC: 24167 AN: 32946 Hom.: 9106 Cov.: 0 AF XY: 0.727 AC XY: 12819 AN XY: 17632

Gnomad4 AFR exome AF: 0.821

Gnomad4 AMR exome AF: 0.821

Gnomad4 ASJ exome AF: 0.780

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.647

Gnomad4 FIN exome AF: 0.684

Gnomad4 NFE exome AF: 0.742

Gnomad4 OTH exome AF: 0.759

GnomAD4 genome AF: 0.759 AC: 115472 AN: 152068 Hom.: 43988 Cov.: 32 AF XY: 0.755 AC XY: 56109 AN XY: 74318

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.770

Alfa AF: 0.749 Hom.: 40837

Bravo AF: 0.773

Asia WGS AF: 0.673 AC: 2342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.83

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: rs769395; hg19: chr2-171716803;