rs8050843

Positions:

• chr16-9836723-T-C

Variant summary

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

The NM_001134407.3(GRIN2A):​c.1652-2493A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,138 control chromosomes in the GnomAD database, including 11,276 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 0.36 (11276 hom., cov: 33)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2A	NM_001134407.3	c.1652-2493A>G		intron_variant		ENST00000330684.4	NP_001127879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2A	ENST00000330684.4	c.1652-2493A>G		intron_variant		1	NM_001134407.3	ENSP00000332549	P1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54169 AN: 152020 Hom.: 11244 Cov.: 33

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0730

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.357 AC: 54243 AN: 152138 Hom.: 11276 Cov.: 33 AF XY: 0.349 AC XY: 25925 AN XY: 74388

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.0732

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.333

Alfa AF: 0.320 Hom.: 1998

Bravo AF: 0.367

Asia WGS AF: 0.170 AC: 598 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	1.1
DANN	Benign	0.28

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: rs8050843; hg19: chr16-9930580;