rs3026160

Variant names:

• chr12-13567109-G-A
• rs3026160
• NM_000834.5:c.2514C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-13567109-G-A
• chr12-13567109-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000834.5(GRIN2B):​c.2514C>T​(p.Cys838Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,670 control chromosomes in the GnomAD database, including 12,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (689 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11809 hom.)
• Consequence: GRIN2B NM_000834.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.648
• Publications: 23 publications found

Genes affected

GRIN2B (HGNC:4586): (glutamate ionotropic receptor NMDA type subunit 2B) This gene encodes a member of the N-methyl-D-aspartate (NMDA) receptor family within the ionotropic glutamate receptor superfamily. The encoded protein is a subunit of the NMDA receptor ion channel which acts as an agonist binding site for glutamate. The NMDA receptors mediate a slow calcium-permeable component of excitatory synaptic transmission in the central nervous system. The NMDA receptors are heterotetramers of seven genetically encoded, differentially expressed subunits including NR1 (GRIN1), NR2 (GRIN2A, GRIN2B, GRIN2C, or GRIN2D) and NR3 (GRIN3A or GRIN3B). The early expression of this gene in development suggests a role in brain development, circuit formation, synaptic plasticity, and cellular migration and differentiation. Naturally occurring mutations within this gene are associated with neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, and schizophrenia. [provided by RefSeq, Aug 2017]

GRIN2B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• developmental and epileptic encephalopathy, 27

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• intellectual disability, autosomal dominant 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-13567109-G-A is Benign according to our data. Variant chr12-13567109-G-A is described in ClinVar as Benign. ClinVar VariationId is 129202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.648 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000834.5. 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
	GRIN2B	NM_000834.5	MANE Select	c.2514C>T	p.Cys838Cys	synonymous	Exon 13 of 14	NP_000825.2	Q13224
	GRIN2B	NM_001413992.1		c.2514C>T	p.Cys838Cys	synonymous	Exon 14 of 15	NP_001400921.1	A0A8D9PHB2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2B	ENST00000609686.4	TSL:1 MANE Select	c.2514C>T	p.Cys838Cys	synonymous	Exon 13 of 14	ENSP00000477455.1	Q13224
	GRIN2B	ENST00000630791.3	TSL:5	c.2514C>T	p.Cys838Cys	synonymous	Exon 14 of 15	ENSP00000486677.3	A0A0D9SFK0
	GRIN2B	ENST00000637214.1	TSL:5	c.69+41494C>T		intron	N/A	ENSP00000489997.1	A0A1B0GU78

Frequencies

GnomAD3 genomes AF: 0.0807 AC: 12285 AN: 152160 Hom.: 689 Cov.: 32

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.0786

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0890

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.0685

GnomAD2 exomes AF: 0.0858 AC: 21581 AN: 251480 AF XY: 0.0892

Gnomad AFR exome AF: 0.0195

Gnomad AMR exome AF: 0.0416

Gnomad ASJ exome AF: 0.0727

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0860

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.0971

GnomAD4 exome AF: 0.120 AC: 174886 AN: 1461392 Hom.: 11809 Cov.: 32 AF XY: 0.118 AC XY: 85758 AN XY: 727028

African (AFR) AF: 0.0178 AC: 597 AN: 33480

American (AMR) AF: 0.0443 AC: 1982 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0757 AC: 1979 AN: 26136

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39700

South Asian (SAS) AF: 0.0686 AC: 5914 AN: 86252

European-Finnish (FIN) AF: 0.0893 AC: 4773 AN: 53420

Middle Eastern (MID) AF: 0.0555 AC: 320 AN: 5766

European-Non Finnish (NFE) AF: 0.138 AC: 153039 AN: 1111526

Other (OTH) AF: 0.104 AC: 6267 AN: 60388

GnomAD4 genome AF: 0.0807 AC: 12285 AN: 152278 Hom.: 689 Cov.: 32 AF XY: 0.0766 AC XY: 5702 AN XY: 74468

African (AFR) AF: 0.0226 AC: 938 AN: 41568

American (AMR) AF: 0.0557 AC: 852 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0786 AC: 273 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0633 AC: 305 AN: 4820

European-Finnish (FIN) AF: 0.0890 AC: 945 AN: 10616

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8751 AN: 68006

Other (OTH) AF: 0.0678 AC: 143 AN: 2110

Alfa AF: 0.0919 Hom.: 2225

Bravo AF: 0.0764

Asia WGS AF: 0.0290 AC: 104 AN: 3478

EpiCase AF: 0.118

EpiControl AF: 0.122

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Inborn genetic diseases (1)
-	-	1	Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.7
DANN	Benign	0.46
PhyloP100		-0.65
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3026160; hg19: chr12-13720043; COSMIC: COSV74207111; COSMIC: COSV74207111;