NM_000835.6:c.399+660C>T

Variant names:

• chr17-74854034-G-A
• rs690533
• NM_000835.6:c.399+660C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000835.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2C	NM_000835.6	MANE Select	c.399+660C>T		intron	N/A	NP_000826.2	Q14957
	GRIN2C	NM_001278553.2		c.399+660C>T		intron	N/A	NP_001265482.1	H0Y2V8
	GRIN2C	NR_103735.2		n.556+660C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2C	ENST00000293190.10	TSL:1 MANE Select	c.399+660C>T		intron	N/A	ENSP00000293190.5	Q14957
	GRIN2C	ENST00000347612.4	TSL:1	c.399+660C>T		intron	N/A	ENSP00000338645.4	H0Y2V8
	GRIN2C	ENST00000584496.1	TSL:1	n.1467C>T		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 1.00 AC: 4 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.625 AC: 5 AN: 8

South Asian (SAS) AF: 0.500 AC: 4 AN: 8

European-Finnish (FIN) AF: 0.726 AC: 45 AN: 62

Middle Eastern (MID) AF: 0.688 AC: 11 AN: 16

European-Non Finnish (NFE) AF: 0.739 AC: 164 AN: 222

Other (OTH) AF: 0.767 AC: 23 AN: 30

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

African (AFR) AF: 0.709 AC: 29407 AN: 41488

American (AMR) AF: 0.788 AC: 12060 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2171 AN: 3470

East Asian (EAS) AF: 0.587 AC: 3030 AN: 5162

South Asian (SAS) AF: 0.735 AC: 3546 AN: 4826

European-Finnish (FIN) AF: 0.751 AC: 7956 AN: 10598

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50751 AN: 67962

Other (OTH) AF: 0.726 AC: 1533 AN: 2112

Alfa AF: 0.742 Hom.: 6731

Bravo AF: 0.730

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
PhyloP100		0.085
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

Other links and lift over

dbSNP: rs690533; hg19: chr17-72850173;