chr9-137156924-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
complex neurodevelopmental disorder
Inheritance: AR, AD Classification: DEFINITIVE Submitted by: ClinGen
neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: G2P, Ambry Genetics
developmental and epileptic encephalopathy 101
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GRIN1 links:

LOC105376328 (HGNC:):

LOC105376328 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 129183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
GRIN1	NM_007327.4 link	c.855G>A	p.Val285Val	synonymous_variant	Exon 6 of 20	ENST00000371561.8	NP_015566.1	Q05586-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN1	ENST00000371561.8 link	c.855G>A	p.Val285Val	synonymous_variant	Exon 6 of 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

GnomAD2 exomes

AF:

0.259

AC:

62818

AN:

242252

AF XY:

0.264

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 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

African (AFR)

AF:

0.0537

AC:

1798

AN:

33466

American (AMR)

AF:

0.197

AC:

8802

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

6829

AN:

26102

East Asian (EAS)

AF:

0.00134

AC:

AN:

39684

South Asian (SAS)

AF:

0.228

AC:

19664

AN:

86206

European-Finnish (FIN)

AF:

0.412

AC:

21301

AN:

51714

Middle Eastern (MID)

AF:

0.279

AC:

1608

AN:

5762

European-Non Finnish (NFE)

AF:

0.327

AC:

363811

AN:

1111448

Other (OTH)

AF:

0.268

AC:

16170

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

18786

37572

56359

75145

93931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11320

22640

33960

45280

56600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.234

AC:

35634

AN:

152264

Hom.:

5431

Cov.:

AF XY:

0.236

AC XY:

17580

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0647

AC:

2690

AN:

41570

American (AMR)

AF:

0.224

AC:

3431

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

886

AN:

3468

East Asian (EAS)

AF:

0.00309

AC:

AN:

5186

South Asian (SAS)

AF:

0.209

AC:

1010

AN:

4824

European-Finnish (FIN)

AF:

0.404

AC:

4285

AN:

10608

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.329

AC:

22383

AN:

67986

Other (OTH)

AF:

0.213

AC:

450

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1353

2706

4060

5413

6766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.275

Hom.:

5438

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

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

Jan 07, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

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

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Dec 31, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over