rs7204266

Positions:

• chr16-9874646-A-G

Variant summary

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

The NM_001134407.3(GRIN2A):​c.1122+16340T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,072 control chromosomes in the GnomAD database, including 11,346 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 (11346 hom., cov: 32)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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 (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2A	NM_001134407.3	c.1122+16340T>C		intron_variant		ENST00000330684.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2A	ENST00000330684.4	c.1122+16340T>C		intron_variant		1	NM_001134407.3	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54399 AN: 151952 Hom.: 11319 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.358 AC: 54476 AN: 152072 Hom.: 11346 Cov.: 32 AF XY: 0.351 AC XY: 26075 AN XY: 74336

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.346

Alfa AF: 0.316 Hom.: 4332

Bravo AF: 0.371

Asia WGS AF: 0.238 AC: 834 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	4.2
DANN	Benign	0.55

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: rs7204266; hg19: chr16-9968503;