rs7972662

Positions:

• chr12-13690538-A-C
• chr12-13690538-A-G
• chr12-13690538-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000609686.4(GRIN2B):​c.1011-14679T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,926 control chromosomes in the GnomAD database, including 23,067 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 0.55 (23067 hom., cov: 31)
• Consequence: GRIN2B ENST00000609686.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.780

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.1011-14679T>G		intron_variant		ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1	c.1011-14679T>G		intron_variant			NP_001400921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.1011-14679T>G		intron_variant		1	NM_000834.5	ENSP00000477455	P1
GRIN2B	ENST00000630791.2	c.1011-14679T>G		intron_variant		5		ENSP00000486677

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83453 AN: 151808 Hom.: 23055 Cov.: 31

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.583

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.550 AC: 83490 AN: 151926 Hom.: 23067 Cov.: 31 AF XY: 0.549 AC XY: 40768 AN XY: 74256

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.583

Alfa AF: 0.529 Hom.: 23371

Bravo AF: 0.553

Asia WGS AF: 0.574 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7972662; hg19: chr12-13843472;