chr16-9844123-T-C

Position:

• chr16-9844123-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.1329-3019A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,982 control chromosomes in the GnomAD database, including 7,773 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 0.32 (7773 hom., cov: 32)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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 = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2A	NM_001134407.3	c.1329-3019A>G		intron_variant		ENST00000330684.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2A	ENST00000330684.4	c.1329-3019A>G		intron_variant		1	NM_001134407.3	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47862 AN: 151862 Hom.: 7768 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.315 AC: 47892 AN: 151982 Hom.: 7773 Cov.: 32 AF XY: 0.308 AC XY: 22901 AN XY: 74292

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.309

Alfa AF: 0.315 Hom.: 1437

Bravo AF: 0.311

Asia WGS AF: 0.204 AC: 713 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	0.71
DANN	Benign	0.51

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: rs12920919; hg19: chr16-9937980;