16-9791170-T-C

Position:

• chr16-9791170-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.2356+7107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,960 control chromosomes in the GnomAD database, including 11,536 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 0.37 (11536 hom., cov: 32)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858

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]

LOC105371077 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2A	NM_001134407.3	c.2356+7107A>G		intron_variant		ENST00000330684.4	NP_001127879.1
LOC105371077	XR_933063.4	n.196T>C		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2A	ENST00000330684.4	c.2356+7107A>G		intron_variant		1	NM_001134407.3	ENSP00000332549	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56856 AN: 151842 Hom.: 11512 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.375 AC: 56922 AN: 151960 Hom.: 11536 Cov.: 32 AF XY: 0.369 AC XY: 27418 AN XY: 74264

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.357

Alfa AF: 0.320 Hom.: 16007

Bravo AF: 0.381

Asia WGS AF: 0.262 AC: 915 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.60
DANN	Benign	0.58

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: rs1833161; hg19: chr16-9885027;