Variant 19-1000421-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.19

Variant links:

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]

GRIN3B links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
GRIN3B	NM_138690.3 linkuse as main transcript	c.-17A>G		5_prime_UTR_variant	1/9	ENST00000234389.3	NP_619635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3B	ENST00000234389.3 linkuse as main transcript	c.-17A>G		5_prime_UTR_variant	1/9	1	NM_138690.3	ENSP00000234389	P1
	ENST00000588380.1 linkuse as main transcript	n.270-254T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61057

AN:

151582

Hom.:

12998

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.463

AC XY:

231280

AN XY:

499810

show subpopulations

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.:

AF XY:

0.399

AC XY:

29577

AN XY:

74162

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over