17-74851066-C-T

Variant names:

• chr17-74851066-C-T
• rs7219247
• NM_000835.6:c.1114-299G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

GRIN2C Gene-Disease associations (from GenCC):

• Alzheimer disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GRIN2C	NM_000835.6	c.1114-299G>A		intron_variant	Intron 4 of 12	ENST00000293190.10	NP_000826.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2C	ENST00000293190.10	c.1114-299G>A		intron_variant	Intron 4 of 12	1	NM_000835.6	ENSP00000293190.5
GRIN2C	ENST00000347612.4	c.1114-299G>A		intron_variant	Intron 4 of 11	1		ENSP00000338645.4
GRIN2C	ENST00000584176.1	n.4171G>A		non_coding_transcript_exon_variant	Exon 2 of 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

African (AFR) AF: 0.295 AC: 3041 AN: 10292

American (AMR) AF: 0.197 AC: 2783 AN: 14096

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 3914 AN: 10238

East Asian (EAS) AF: 0.429 AC: 9651 AN: 22474

South Asian (SAS) AF: 0.270 AC: 8050 AN: 29772

European-Finnish (FIN) AF: 0.280 AC: 5340 AN: 19038

Middle Eastern (MID) AF: 0.342 AC: 494 AN: 1444

European-Non Finnish (NFE) AF: 0.272 AC: 51551 AN: 189316

Other (OTH) AF: 0.285 AC: 5434 AN: 19064

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

African (AFR) AF: 0.300 AC: 12447 AN: 41458

American (AMR) AF: 0.218 AC: 3329 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3472

East Asian (EAS) AF: 0.409 AC: 2111 AN: 5158

South Asian (SAS) AF: 0.273 AC: 1316 AN: 4814

European-Finnish (FIN) AF: 0.286 AC: 3033 AN: 10598

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18516 AN: 67960

Other (OTH) AF: 0.287 AC: 603 AN: 2104

Alfa AF: 0.275 Hom.: 6054

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
PhyloP100		0.43
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: rs7219247; hg19: chr17-72847205;