rs2240157

chr19-1004741-T-Cchr19-1004741-T-G

Variant summary

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

The NM_138690.3(GRIN3B):c.1240T>C(p.Trp414Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 1,607,864 control chromosomes in the GnomAD database, including 403,326 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.72 (39300 hom., cov: 34)
  • Exomes 𝑓: 0.70 (364026 hom.)
• Consequence: GRIN3B NM_138690.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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=1.9714284E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3B	NM_138690.3	c.1240T>C	p.Trp414Arg	missense_variant	3/9	ENST00000234389.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3B	ENST00000234389.3	c.1240T>C	p.Trp414Arg	missense_variant	3/9	1	NM_138690.3	P1
GRIN3B	ENST00000588335.1	n.51-61T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108787 AN: 151976 Hom.: 39250 Cov.: 34

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.738

GnomAD3 exomes AF: 0.680 AC: 165352 AN: 243026 Hom.: 57543 AF XY: 0.688 AC XY: 91147 AN XY: 132394

Gnomad AFR exome AF: 0.786

Gnomad AMR exome AF: 0.527

Gnomad ASJ exome AF: 0.798

Gnomad EAS exome AF: 0.492

Gnomad SAS exome AF: 0.743

Gnomad FIN exome AF: 0.700

Gnomad NFE exome AF: 0.712

Gnomad OTH exome AF: 0.698

GnomAD4 exome AF: 0.705 AC: 1026228 AN: 1455768 Hom.: 364026 Cov.: 63 AF XY: 0.707 AC XY: 511438 AN XY: 723454

Gnomad4 AFR exome AF: 0.794

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.799

Gnomad4 EAS exome AF: 0.531

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.705

Gnomad4 NFE exome AF: 0.709

Gnomad4 OTH exome AF: 0.710

GnomAD4 genome AF: 0.716 AC: 108891 AN: 152096 Hom.: 39300 Cov.: 34 AF XY: 0.713 AC XY: 52991 AN XY: 74346

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.742

Alfa AF: 0.705 Hom.: 36378

Bravo AF: 0.709

TwinsUK AF: 0.705 AC: 2613

ALSPAC AF: 0.715 AC: 2755

ESP6500AA AF: 0.786 AC: 3447

ESP6500EA AF: 0.712 AC: 6108

ExAC AF: 0.686 AC: 82899

Asia WGS AF: 0.658 AC: 2292 AN: 3478

EpiCase AF: 0.720

EpiControl AF: 0.729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.1
Dann	Benign	0.44
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.049	T
MetaRNN	Benign	0.0000020	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.6	N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	3.2	N
REVEL	Benign	0.067
Sift	Benign	0.39	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.022
MutPred		0.28		Gain of disorder (P = 0.0016);
MPC		0.20
ClinPred		0.012	T
GERP RS		3.4
Varity_R		0.043
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs2240157; hg19: chr19-1004740; COSMIC: COSV52260707; COSMIC: COSV52260707;