2-170815681-G-T

Position:

• chr2-170815681-G-T

Variant summary

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

The ENST00000663207.1(ENSG00000235934):​n.1143C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,114 control chromosomes in the GnomAD database, including 5,083 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 0.23 (5083 hom., cov: 32)
• Consequence: ENST00000663207.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

Genes affected

(HGNC:):

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAD1	XM_011510922.1	c.-64+2259G>T		intron_variant			XP_011509224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000663207.1	n.1143C>A		non_coding_transcript_exon_variant	2/2
GAD1	ENST00000454603.5	c.-64+2259G>T		intron_variant		4		ENSP00000402366

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35418 AN: 151996 Hom.: 5080 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.233 AC: 35423 AN: 152114 Hom.: 5083 Cov.: 32 AF XY: 0.234 AC XY: 17381 AN XY: 74348

Gnomad4 AFR AF: 0.0644

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.245

Alfa AF: 0.303 Hom.: 9495

Bravo AF: 0.218

Asia WGS AF: 0.280 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.4
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3791878; hg19: chr2-171672191;