rs1969060

chr16-10023280-G-Achr16-10023280-G-C

Variant summary

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

The NM_001134407.3(GRIN2A):c.415-84729C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,104 control chromosomes in the GnomAD database, including 40,783 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 (40783 hom., cov: 32)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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=-0.86).
• 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.415-84729C>T		intron_variant		ENST00000330684.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2A	ENST00000330684.4	c.415-84729C>T		intron_variant		1	NM_001134407.3	P1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 109035 AN: 151986 Hom.: 40765 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.717 AC: 109089 AN: 152104 Hom.: 40783 Cov.: 32 AF XY: 0.713 AC XY: 53035 AN XY: 74350

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.740

Alfa AF: 0.763 Hom.: 5617

Bravo AF: 0.698

Asia WGS AF: 0.542 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	12
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1969060; hg19: chr16-10117137;