2-170814656-C-T

Variant names:

• chr2-170814656-C-T
• rs872123
• ENST00000454603.5:c.-64+1234C>T

Variant summary

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

The ENST00000454603.5(GAD1):​c.-64+1234C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,094 control chromosomes in the GnomAD database, including 33,688 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 0.64 (33688 hom., cov: 32)
• Consequence: GAD1 ENST00000454603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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:40250):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAD1	XM_011510922.1	c.-64+1234C>T		intron_variant	Intron 1 of 16		XP_011509224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAD1	ENST00000454603.5	c.-64+1234C>T		intron_variant	Intron 1 of 3	4		ENSP00000402366.1
ENSG00000235934	ENST00000663207.1	n.*30G>A		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97409 AN: 151976 Hom.: 33672 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.641 AC: 97455 AN: 152094 Hom.: 33688 Cov.: 32 AF XY: 0.644 AC XY: 47876 AN XY: 74376

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.743

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.681

Alfa AF: 0.604 Hom.: 2200

Bravo AF: 0.626

Asia WGS AF: 0.735 AC: 2552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.25
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs872123; hg19: chr2-171671166;