rs8050385

Positions:

• chr16-10025879-C-A
• chr16-10025879-C-G

Variant summary

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

The NM_001134407.3(GRIN2A):​c.415-87328G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,966 control chromosomes in the GnomAD database, including 41,060 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 0.72 (41060 hom., cov: 30)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

Genes affected

GRIN2A (HGNC:4585): (glutamate ionotropic receptor NMDA type subunit 2A) This gene encodes a member of the glutamate-gated ion channel protein family. The encoded protein is an N-methyl-D-aspartate (NMDA) receptor subunit. NMDA receptors are both ligand-gated and voltage-dependent, and are involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. These receptors are permeable to calcium ions, and activation results in a calcium influx into post-synaptic cells, which results in the activation of several signaling cascades. Disruption of this gene is associated with focal epilepsy and speech disorder with or without cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2A	NM_001134407.3	c.415-87328G>T		intron_variant		ENST00000330684.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2A	ENST00000330684.4	c.415-87328G>T		intron_variant		1	NM_001134407.3	P1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109523 AN: 151848 Hom.: 41039 Cov.: 30

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.721 AC: 109591 AN: 151966 Hom.: 41060 Cov.: 30 AF XY: 0.717 AC XY: 53288 AN XY: 74290

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.769

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.836

Gnomad4 OTH AF: 0.742

Alfa AF: 0.807 Hom.: 100372

Bravo AF: 0.703

Asia WGS AF: 0.548 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.66

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: rs8050385; hg19: chr16-10119736;