16-10174473-T-C

Position:

• chr16-10174473-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.414+5525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,058 control chromosomes in the GnomAD database, including 26,453 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 0.58 (26453 hom., cov: 32)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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]

GRIN2A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2A	NM_001134407.3	c.414+5525A>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.414+5525A>G		intron_variant		1	NM_001134407.3	ENSP00000332549.3

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88569 AN: 151940 Hom.: 26443 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.583 AC: 88611 AN: 152058 Hom.: 26453 Cov.: 32 AF XY: 0.581 AC XY: 43183 AN XY: 74314

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.593

Alfa AF: 0.634 Hom.: 51296

Bravo AF: 0.570

Asia WGS AF: 0.497 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.55
DANN	Benign	0.42

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: rs1650420; hg19: chr16-10268330;