12-13982130-T-G

Variant names:

• chr12-13982130-T-G
• rs3764028
• NM_001413992.1:c.-897A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001413992.1(GRIN2B):​c.-897A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 149,630 control chromosomes in the GnomAD database, including 59,314 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 0.89 (59314 hom., cov: 23)
• Consequence: GRIN2B NM_001413992.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413992.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2B	NM_001413992.1		c.-897A>C		5_prime_UTR	Exon 1 of 15	NP_001400921.1
	GRIN2B	NM_001413993.1		c.-468A>C		5_prime_UTR	Exon 1 of 4	NP_001400922.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN2B	ENST00000630791.3	TSL:5	c.-897A>C		upstream_gene	N/A	ENSP00000486677.3
	GRIN2B	ENST00000627535.2	TSL:5	c.-662A>C		upstream_gene	N/A	ENSP00000486411.1

Frequencies

GnomAD3 genomes AF: 0.886 AC: 132459 AN: 149524 Hom.: 59280 Cov.: 23

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.895

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

GnomAD4 genome AF: 0.886 AC: 132543 AN: 149630 Hom.: 59314 Cov.: 23 AF XY: 0.879 AC XY: 64153 AN XY: 72990

African (AFR) AF: 0.764 AC: 30875 AN: 40402

American (AMR) AF: 0.890 AC: 13428 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.983 AC: 3409 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3012 AN: 4788

South Asian (SAS) AF: 0.864 AC: 4074 AN: 4716

European-Finnish (FIN) AF: 0.881 AC: 9127 AN: 10362

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.971 AC: 65590 AN: 67538

Other (OTH) AF: 0.892 AC: 1848 AN: 2072

Alfa AF: 0.919 Hom.: 4956

Bravo AF: 0.879

Asia WGS AF: 0.737 AC: 2553 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.38
PhyloP100		-2.3
PromoterAI		0.062	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3764028; hg19: chr12-14135064;