12-13570458-T-G

Position:

• chr12-13570458-T-G

Variant summary

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

The ENST00000609686.4(GRIN2B):​c.2172-441A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,052 control chromosomes in the GnomAD database, including 20,942 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 0.51 (20942 hom., cov: 33)
• Consequence: GRIN2B ENST00000609686.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2B	NM_000834.5	c.2172-441A>C		intron_variant		ENST00000609686.4	NP_000825.2
GRIN2B	NM_001413992.1	c.2172-441A>C		intron_variant			NP_001400921.1
GRIN2B	XM_005253351.3	c.-43-441A>C		intron_variant			XP_005253408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4	c.2172-441A>C		intron_variant		1	NM_000834.5	ENSP00000477455	P1
GRIN2B	ENST00000637214.1	c.69+38145A>C		intron_variant		5		ENSP00000489997
GRIN2B	ENST00000628166.2	n.432-441A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78170 AN: 151934 Hom.: 20915 Cov.: 33

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.515 AC: 78238 AN: 152052 Hom.: 20942 Cov.: 33 AF XY: 0.525 AC XY: 38992 AN XY: 74334

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.530

Alfa AF: 0.404 Hom.: 1652

Bravo AF: 0.506

Asia WGS AF: 0.825 AC: 2865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.76

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: rs1806195; hg19: chr12-13723392;