rs8057394

chr16-10021631-C-G

Variant summary

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

The NM_001134407.3(GRIN2A):c.415-83080G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,950 control chromosomes in the GnomAD database, including 32,918 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 0.65 (32918 hom., cov: 31)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2A	NM_001134407.3	c.415-83080G>C		intron_variant		ENST00000330684.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2A	ENST00000330684.4	c.415-83080G>C		intron_variant		1	NM_001134407.3	P1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98369 AN: 151832 Hom.: 32906 Cov.: 31

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.648 AC: 98419 AN: 151950 Hom.: 32918 Cov.: 31 AF XY: 0.647 AC XY: 48056 AN XY: 74306

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.694

Alfa AF: 0.680 Hom.: 4448

Bravo AF: 0.634

Asia WGS AF: 0.575 AC: 1998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.29
Dann	Benign	0.37

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: rs8057394; hg19: chr16-10115488;