rs1126442

Positions:

chr9-137156924-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_007327.4(GRIN1):c.855G>A(p.Val285Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,611,588 control chromosomes in the GnomAD database, including 76,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5431 hom., cov: 34)

Exomes 𝑓: 0.30 ( 70985 hom. )

Consequence

GRIN1
NM_007327.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

GRIN1 (HGNC:4584): (glutamate ionotropic receptor NMDA type subunit 1) The protein encoded by this gene is a critical subunit of N-methyl-D-aspartate receptors, members of the glutamate receptor channel superfamily which are heteromeric protein complexes with multiple subunits arranged to form a ligand-gated ion channel. These subunits play a key role in the plasticity of synapses, which is believed to underlie memory and learning. Cell-specific factors are thought to control expression of different isoforms, possibly contributing to the functional diversity of the subunits. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

GRIN1 links:

LOC105376328 (HGNC:):

LOC105376328 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 9-137156924-G-A is Benign according to our data. Variant chr9-137156924-G-A is described in ClinVar as [Benign]. Clinvar id is 129183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137156924-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN1	NM_007327.4 link	c.855G>A	p.Val285Val	synonymous_variant	6/20	ENST00000371561.8	NP_015566.1	Q05586-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN1	ENST00000371561.8 link	c.855G>A	p.Val285Val	synonymous_variant	6/20	1	NM_007327.4	ENSP00000360616.3		Q05586-1

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35633

AN:

152146

Hom.:

5430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0649

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.215

GnomAD3 exomes

AF:

0.259

AC:

62818

AN:

242252

Hom.:

9756

AF XY:

0.264

AC XY:

34870

AN XY:

132056

show subpopulations

Gnomad AFR exome

AF:

0.0559

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.00165

Gnomad SAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.415

Gnomad NFE exome

AF:

0.331

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.302

AC:

440036

AN:

1459324

Hom.:

70985

Cov.:

AF XY:

0.300

AC XY:

217435

AN XY:

725956

show subpopulations

Gnomad4 AFR exome

AF:

0.0537

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.262

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.228

Gnomad4 FIN exome

AF:

0.412

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.268

GnomAD4 genome

AF:

0.234

AC:

35634

AN:

152264

Hom.:

5431

Cov.:

AF XY:

0.236

AC XY:

17580

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0647

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.255

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.404

Gnomad4 NFE

AF:

0.329

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.290

Hom.:

4281

Bravo

AF:

0.212

Asia WGS

AF:

0.0890

AC:

311

AN:

3478

EpiCase

AF:

0.318

EpiControl

AF:

0.319

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 07, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 45. Only high quality variants are reported. -

Intellectual disability, autosomal dominant 8

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 31, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.97

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

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