rs11866570

Positions:

• chr16-10112318-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+67680A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 643,826 control chromosomes in the GnomAD database, including 4,843 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 0.13 (1519 hom., cov: 34)
  • Exomes 𝑓: 0.10 (3324 hom.)
• Consequence: GRIN2A NM_001134407.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811

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]

IMPDH1P11 (HGNC:6054): (inosine monophosphate dehydrogenase 1 pseudogene 11)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2A	NM_001134407.3	c.414+67680A>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+67680A>G		intron_variant		1	NM_001134407.3	ENSP00000332549	P1
IMPDH1P11	ENST00000567885.1	n.937T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20217 AN: 152198 Hom.: 1519 Cov.: 34

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0167

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.104 AC: 51000 AN: 491510 Hom.: 3324 Cov.: 0 AF XY: 0.0987 AC XY: 26212 AN XY: 265670

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.0593

Gnomad4 ASJ exome AF: 0.0426

Gnomad4 EAS exome AF: 0.000217

Gnomad4 SAS exome AF: 0.0162

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.133 AC: 20238 AN: 152316 Hom.: 1519 Cov.: 34 AF XY: 0.130 AC XY: 9697 AN XY: 74496

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.0888

Gnomad4 ASJ AF: 0.0447

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.114

Alfa AF: 0.121 Hom.: 2318

Bravo AF: 0.128

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.15
DANN	Benign	0.25

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: rs11866570; hg19: chr16-10206175;