rs690533

chr17-74854034-G-Achr17-74854034-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000835.6(GRIN2C):c.399+660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 152,470 control chromosomes in the GnomAD database, including 41,111 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 0.73 (41016 hom., cov: 33)
  • Exomes 𝑓: 0.73 (95 hom.)
• Consequence: GRIN2C NM_000835.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

Genes affected

GRIN2C (HGNC:4587): (glutamate ionotropic receptor NMDA type subunit 2C) This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptor, which is a subtype of ionotropic glutamate receptor. NMDA receptors are found in the central nervous system, are permeable to cations and have an important role in physiological processes such as learning, memory, and synaptic development. The receptor is a tetramer of different subunits (typically heterodimer of subunit 1 with one or more of subunits 2A-D), forming a channel that is permeable to calcium, potassium, and sodium, and whose properties are determined by subunit composition. Alterations in the subunit composition of the receptor are associated with pathophysiological conditions such as Parkinson's disease, Alzheimer's disease, depression, and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2C	NM_000835.6	c.399+660C>T		intron_variant		ENST00000293190.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN2C	ENST00000293190.10	c.399+660C>T		intron_variant		1	NM_000835.6	P1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111288 AN: 152000 Hom.: 40982 Cov.: 33

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.727 AC: 256 AN: 352 Hom.: 95 Cov.: 0 AF XY: 0.728 AC XY: 166 AN XY: 228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.625

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.726

Gnomad4 NFE exome AF: 0.739

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.732 AC: 111374 AN: 152118 Hom.: 41016 Cov.: 33 AF XY: 0.735 AC XY: 54639 AN XY: 74356

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.726

Alfa AF: 0.742 Hom.: 6731

Bravo AF: 0.730

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs690533; hg19: chr17-72850173;