rs4807399

Positions:

• chr19-1004711-C-T

Variant summary

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

The NM_138690.3(GRIN3B):​c.1210C>T​(p.Arg404Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,602,780 control chromosomes in the GnomAD database, including 205,128 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.45 (16115 hom., cov: 33)
  • Exomes 𝑓: 0.50 (189013 hom.)
• Consequence: GRIN3B NM_138690.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942

Genes affected

GRIN3B (HGNC:16768): (glutamate ionotropic receptor NMDA type subunit 3B) The protein encoded by this gene is a subunit of an N-methyl-D-aspartate (NMDA) receptor. The encoded protein is found primarily in motor neurons, where it forms a heterotetramer with GRIN1 to create an excitatory glycine receptor. Variations in this gene have been proposed to be linked to schizophrenia. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2913346E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3B	NM_138690.3	c.1210C>T	p.Arg404Trp	missense_variant	3/9	ENST00000234389.3	NP_619635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3B	ENST00000234389.3	c.1210C>T	p.Arg404Trp	missense_variant	3/9	1	NM_138690.3	ENSP00000234389	P1
GRIN3B	ENST00000588335.1	n.51-91C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68868 AN: 151916 Hom.: 16110 Cov.: 33

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.0858

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.443

GnomAD3 exomes AF: 0.443 AC: 103970 AN: 234738 Hom.: 24562 AF XY: 0.452 AC XY: 57949 AN XY: 128146

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.477

Gnomad EAS exome AF: 0.0809

Gnomad SAS exome AF: 0.454

Gnomad FIN exome AF: 0.481

Gnomad NFE exome AF: 0.525

Gnomad OTH exome AF: 0.454

GnomAD4 exome AF: 0.503 AC: 729752 AN: 1450746 Hom.: 189013 Cov.: 62 AF XY: 0.503 AC XY: 362252 AN XY: 720390

Gnomad4 AFR exome AF: 0.384

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.0874

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.474

GnomAD4 genome AF: 0.453 AC: 68900 AN: 152034 Hom.: 16115 Cov.: 33 AF XY: 0.450 AC XY: 33404 AN XY: 74308

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.0861

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.439

Alfa AF: 0.503 Hom.: 6015

Bravo AF: 0.442

TwinsUK AF: 0.527 AC: 1955

ALSPAC AF: 0.537 AC: 2071

ESP6500AA AF: 0.398 AC: 1746

ESP6500EA AF: 0.520 AC: 4461

ExAC AF: 0.442 AC: 53352

Asia WGS AF: 0.265 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.6
DANN	Benign	0.82
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.00013	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.90	N
REVEL	Benign	0.013
Sift	Benign	0.060	T
Sift4G	Uncertain	0.010	D
Polyphen		0.033	B
Vest4		0.12
MPC		0.12
ClinPred		0.0091	T
GERP RS		-3.3
Varity_R		0.053
gMVP		0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs4807399; hg19: chr19-1004710; COSMIC: COSV52259202; COSMIC: COSV52259202;