dbSNP rs690533: GRIN2C:n.1467C>T (chr17-74854034-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000584496.1(GRIN2C):n.1467C>T variant causes a non coding transcript exon 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
ENST00000584496.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850

Publications

6 publications found

Variant links:

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

GRIN2C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2C	NM_000835.6 link	c.399+660C>T		intron_variant	Intron 2 of 12	ENST00000293190.10	NP_000826.2	Q14957A0A8D9PH81O15398

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2C	ENST00000293190.10 link	c.399+660C>T		intron_variant	Intron 2 of 12	1	NM_000835.6	ENSP00000293190.5		Q14957

Frequencies

GnomAD3 genomes

AF:

0.732

AC:

111288

AN:

152000

Hom.:

40982

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.728

AC XY:

166

AN XY:

228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.625

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.726

AC:

AN:

Middle Eastern (MID)

AF:

0.688

AC:

AN:

European-Non Finnish (NFE)

AF:

0.739

AC:

164

AN:

222

Other (OTH)

AF:

0.767

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.732

AC:

111374

AN:

152118

Hom.:

41016

Cov.:

AF XY:

0.735

AC XY:

54639

AN XY:

74356

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1521

3042

4562

6083

7604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

848

1696

2544

3392

4240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over