rs4998386

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001134407.3(GRIN2A):​c.415-38137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,156 control chromosomes in the GnomAD database, including 1,154 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 0.11 ( 1154 hom., cov: 32)

Consequence

GRIN2A
NM_001134407.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIN2ANM_001134407.3 linkuse as main transcriptc.415-38137G>A intron_variant ENST00000330684.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIN2AENST00000330684.4 linkuse as main transcriptc.415-38137G>A intron_variant 1 NM_001134407.3 P1Q12879-1

Frequencies

GnomAD3 genomes
AF:
0.110
AC:
16767
AN:
152038
Hom.:
1155
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.176
Gnomad AMI
AF:
0.0143
Gnomad AMR
AF:
0.0604
Gnomad ASJ
AF:
0.0311
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0110
Gnomad FIN
AF:
0.122
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.102
Gnomad OTH
AF:
0.0827
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.110
AC:
16779
AN:
152156
Hom.:
1154
Cov.:
32
AF XY:
0.107
AC XY:
7922
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.175
Gnomad4 AMR
AF:
0.0604
Gnomad4 ASJ
AF:
0.0311
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0112
Gnomad4 FIN
AF:
0.122
Gnomad4 NFE
AF:
0.102
Gnomad4 OTH
AF:
0.0818
Alfa
AF:
0.0994
Hom.:
360
Bravo
AF:
0.109
Asia WGS
AF:
0.0150
AC:
52
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.40
DANN
Benign
0.44

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4998386; hg19: chr16-10070545; API