NM_001134407.3:c.414+67680A>G

Variant names:

• chr16-10112318-T-C
• rs11866570
• NM_001134407.3:c.414+67680A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134407.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2A	NM_001134407.3	MANE Select	c.414+67680A>G		intron	N/A	NP_001127879.1
	GRIN2A	NM_000833.5		c.414+67680A>G		intron	N/A	NP_000824.1
	GRIN2A	NM_001134408.2		c.414+67680A>G		intron	N/A	NP_001127880.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2A	ENST00000330684.4	TSL:1 MANE Select	c.414+67680A>G		intron	N/A	ENSP00000332549.3
	GRIN2A	ENST00000396573.6	TSL:1	c.414+67680A>G		intron	N/A	ENSP00000379818.2
	GRIN2A	ENST00000562109.5	TSL:1	c.414+67680A>G		intron	N/A	ENSP00000454998.1

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

African (AFR) AF: 0.177 AC: 2450 AN: 13860

American (AMR) AF: 0.0593 AC: 1647 AN: 27754

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 578 AN: 13556

East Asian (EAS) AF: 0.000217 AC: 7 AN: 32202

South Asian (SAS) AF: 0.0162 AC: 874 AN: 53816

European-Finnish (FIN) AF: 0.156 AC: 5691 AN: 36556

Middle Eastern (MID) AF: 0.0181 AC: 44 AN: 2426

European-Non Finnish (NFE) AF: 0.130 AC: 36935 AN: 284994

Other (OTH) AF: 0.105 AC: 2774 AN: 26346

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

African (AFR) AF: 0.180 AC: 7495 AN: 41554

American (AMR) AF: 0.0888 AC: 1359 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4834

European-Finnish (FIN) AF: 0.170 AC: 1802 AN: 10626

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9050 AN: 68022

Other (OTH) AF: 0.114 AC: 241 AN: 2116

Alfa AF: 0.125 Hom.: 3910

Bravo AF: 0.128

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.15
DANN	Benign	0.25
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11866570; hg19: chr16-10206175;