19-1000421-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138690.3(GRIN3B):c.-17A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,209,810 control chromosomes in the GnomAD database, including 128,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12990 hom., cov: 32)
  • Exomes 𝑓: 0.46 (115176 hom.)
• Consequence: GRIN3B NM_138690.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-1000421-A-G is Benign according to our data. Variant chr19-1000421-A-G is described in ClinVar as [Benign]. Clinvar id is 1285692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3B	NM_138690.3	c.-17A>G		5_prime_UTR_variant	1/9	ENST00000234389.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3B	ENST00000234389.3	c.-17A>G		5_prime_UTR_variant	1/9	1	NM_138690.3	P1
	ENST00000588380.1	n.270-254T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61057 AN: 151582 Hom.: 12998 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.393

GnomAD3 exomes AF: 0.305 AC: 2396 AN: 7860 Hom.: 405 AF XY: 0.303 AC XY: 1358 AN XY: 4482

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.290

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.164

Gnomad SAS exome AF: 0.174

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.352

Gnomad OTH exome AF: 0.350

GnomAD4 exome AF: 0.463 AC: 489578 AN: 1058120 Hom.: 115176 Cov.: 32 AF XY: 0.463 AC XY: 231280 AN XY: 499810

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.402 AC: 61052 AN: 151690 Hom.: 12990 Cov.: 32 AF XY: 0.399 AC XY: 29577 AN XY: 74162

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.390

Alfa AF: 0.434 Hom.: 1837

Bravo AF: 0.396

Asia WGS AF: 0.266 AC: 918 AN: 3436

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.8
Dann	Benign	0.34

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: rs112743753; hg19: chr19-1000420; COSMIC: COSV52261285; COSMIC: COSV52261285;