rs689730

Variant names:

• chr17-74854994-G-A
• rs689730
• NM_000835.6:c.99C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-74854994-G-A
• chr17-74854994-G-C
• chr17-74854994-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000835.6(GRIN2C):​c.99C>T​(p.Ala33Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,607,346 control chromosomes in the GnomAD database, including 12,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1791 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10701 hom.)
• Consequence: GRIN2C NM_000835.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.419
• Publications: 24 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-74854994-G-A is Benign according to our data. Variant chr17-74854994-G-A is described in ClinVar as Benign. ClinVar VariationId is 769223.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.419 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2C	NM_000835.6	c.99C>T	p.Ala33Ala	synonymous_variant	Exon 2 of 13	ENST00000293190.10	NP_000826.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2C	ENST00000293190.10	c.99C>T	p.Ala33Ala	synonymous_variant	Exon 2 of 13	1	NM_000835.6	ENSP00000293190.5

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20988 AN: 152044 Hom.: 1782 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0708

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.109 AC: 158687 AN: 1455184 Hom.: 10701 Cov.: 32 AF XY: 0.113 AC XY: 81609 AN XY: 724190

African (AFR) AF: 0.182 AC: 6080 AN: 33470

American (AMR) AF: 0.203 AC: 9056 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 3192 AN: 26092

East Asian (EAS) AF: 0.251 AC: 9937 AN: 39656

South Asian (SAS) AF: 0.230 AC: 19789 AN: 86190

European-Finnish (FIN) AF: 0.0708 AC: 3365 AN: 47542

Middle Eastern (MID) AF: 0.250 AC: 1419 AN: 5682

European-Non Finnish (NFE) AF: 0.0878 AC: 97560 AN: 1111684

Other (OTH) AF: 0.138 AC: 8289 AN: 60282

GnomAD4 genome AF: 0.138 AC: 21022 AN: 152162 Hom.: 1791 Cov.: 33 AF XY: 0.141 AC XY: 10476 AN XY: 74376

African (AFR) AF: 0.179 AC: 7434 AN: 41486

American (AMR) AF: 0.206 AC: 3149 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3468

East Asian (EAS) AF: 0.246 AC: 1271 AN: 5174

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4826

European-Finnish (FIN) AF: 0.0708 AC: 752 AN: 10616

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.0927 AC: 6300 AN: 67976

Other (OTH) AF: 0.163 AC: 345 AN: 2112

Alfa AF: 0.117 Hom.: 3342

Bravo AF: 0.147

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 14, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.5
PhyloP100		-0.42

Splicing

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

Other links and lift over

dbSNP: rs689730; hg19: chr17-72851133;