rs890

Variant names:

• chr12-13562374-A-C
• rs890
• NM_000834.5:c.*409T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-13562374-A-C
• chr12-13562374-A-G
• chr12-13562374-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000834.5(GRIN2B):​c.*409T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 199,382 control chromosomes in the GnomAD database, including 17,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (13159 hom., cov: 32)
  • Exomes 𝑓: 0.42 (4765 hom.)
• Consequence: GRIN2B NM_000834.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0780
• Publications: 54 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: Labcorp Genetics (formerly Invitae), G2P
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-13562374-A-C is Benign according to our data. Variant chr12-13562374-A-C is described in ClinVar as Benign. ClinVar VariationId is 1281683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.*409T>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1	c.*409T>G		3_prime_UTR_variant	Exon 15 of 15		NP_001400921.1
GRIN2B	XM_005253351.3	c.*409T>G		3_prime_UTR_variant	Exon 4 of 4		XP_005253408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.*409T>G		3_prime_UTR_variant	Exon 14 of 14	1	NM_000834.5	ENSP00000477455.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57427 AN: 151944 Hom.: 13156 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.424 AC: 20070 AN: 47320 Hom.: 4765 Cov.: 0 AF XY: 0.421 AC XY: 10003 AN XY: 23770

African (AFR) AF: 0.0884 AC: 129 AN: 1460

American (AMR) AF: 0.497 AC: 1827 AN: 3674

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 526 AN: 1102

East Asian (EAS) AF: 0.209 AC: 599 AN: 2868

South Asian (SAS) AF: 0.282 AC: 1308 AN: 4642

European-Finnish (FIN) AF: 0.407 AC: 756 AN: 1858

Middle Eastern (MID) AF: 0.533 AC: 80 AN: 150

European-Non Finnish (NFE) AF: 0.473 AC: 13660 AN: 28876

Other (OTH) AF: 0.441 AC: 1185 AN: 2690

GnomAD4 genome AF: 0.378 AC: 57432 AN: 152062 Hom.: 13159 Cov.: 32 AF XY: 0.375 AC XY: 27860 AN XY: 74312

African (AFR) AF: 0.115 AC: 4785 AN: 41480

American (AMR) AF: 0.485 AC: 7407 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1791 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1116 AN: 5168

South Asian (SAS) AF: 0.293 AC: 1412 AN: 4816

European-Finnish (FIN) AF: 0.434 AC: 4585 AN: 10556

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34855 AN: 67972

Other (OTH) AF: 0.436 AC: 919 AN: 2110

Alfa AF: 0.463 Hom.: 51913

Bravo AF: 0.374

Asia WGS AF: 0.250 AC: 872 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26257337) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		0.078
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs890; hg19: chr12-13715308;