rs7201930

Positions:

• chr16-9864798-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.1123-14837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,022 control chromosomes in the GnomAD database, including 12,746 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 0.38 (12746 hom., cov: 32)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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 = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2A	NM_001134407.3	c.1123-14837A>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.1123-14837A>G		intron_variant		1	NM_001134407.3	ENSP00000332549	P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58347 AN: 151904 Hom.: 12720 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.384 AC: 58422 AN: 152022 Hom.: 12746 Cov.: 32 AF XY: 0.376 AC XY: 27959 AN XY: 74306

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.362

Alfa AF: 0.335 Hom.: 4154

Bravo AF: 0.394

Asia WGS AF: 0.229 AC: 800 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7201930; hg19: chr16-9958655;