17-74851066-C-T

Position:

• chr17-74851066-C-T

Variant summary

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

The NM_000835.6(GRIN2C):​c.1114-299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 467,806 control chromosomes in the GnomAD database, including 19,781 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 0.28 (6301 hom., cov: 32)
  • Exomes 𝑓: 0.29 (13480 hom.)
• Consequence: GRIN2C NM_000835.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2C	NM_000835.6	c.1114-299G>A		intron_variant		ENST00000293190.10	NP_000826.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2C	ENST00000293190.10	c.1114-299G>A		intron_variant		1	NM_000835.6	ENSP00000293190.5
GRIN2C	ENST00000347612.4	c.1114-299G>A		intron_variant		1		ENSP00000338645.4
GRIN2C	ENST00000584176.1	n.4171G>A		non_coding_transcript_exon_variant	2/9	2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42951 AN: 151952 Hom.: 6290 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.286 AC: 90258 AN: 315734 Hom.: 13480 Cov.: 0 AF XY: 0.285 AC XY: 46557 AN XY: 163532

Gnomad4 AFR exome AF: 0.295

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.280

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.283 AC: 42992 AN: 152072 Hom.: 6301 Cov.: 32 AF XY: 0.280 AC XY: 20812 AN XY: 74346

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.287

Alfa AF: 0.274 Hom.: 5058

Bravo AF: 0.282

Asia WGS AF: 0.308 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.55

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: rs7219247; hg19: chr17-72847205;