rs116006955

Positions:

chr9-137162040-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_007327.4(GRIN1):c.1584G>A(p.Glu528Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000889 in 1,448,032 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 7 hom., cov: 31)

Exomes 𝑓: 0.00047 ( 6 hom. )

Consequence

GRIN1
NM_007327.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.51

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:

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=-0.45).

BP6

Variant 9-137162040-G-A is Benign according to our data. Variant chr9-137162040-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 383234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137162040-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=3.51 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00466 (671/144130) while in subpopulation AFR AF= 0.016 (637/39704). AF 95% confidence interval is 0.015. There are 7 homozygotes in gnomad4. There are 330 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN1	NM_007327.4 link	c.1584G>A	p.Glu528Glu	synonymous_variant	11/20	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.1584G>A	p.Glu528Glu	synonymous_variant	11/20	1	NM_007327.4	ENSP00000360616.3		Q05586-1

Frequencies

GnomAD3 genomes

AF:

0.00466

AC:

671

AN:

144010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00153

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000700

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000761

Gnomad OTH

AF:

0.00249

GnomAD3 exomes

AF:

0.000946

AC:

154

AN:

162818

Hom.:

AF XY:

0.000650

AC XY:

AN XY:

86148

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.000709

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000432

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000156

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000473

AC:

617

AN:

1303902

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

252

AN XY:

641776

show subpopulations

Gnomad4 AFR exome

AF:

0.0180

Gnomad4 AMR exome

AF:

0.000813

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000508

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000787

Gnomad4 OTH exome

AF:

0.00102

GnomAD4 genome

AF:

0.00466

AC:

671

AN:

144130

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

330

AN XY:

69920

show subpopulations

Gnomad4 AFR

AF:

0.0160

Gnomad4 AMR

AF:

0.00153

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000467

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000761

Gnomad4 OTH

AF:

0.00246

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.00503

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 09, 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. -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Sep 15, 2016	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 25, 2018	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2016

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. -

Intellectual disability, autosomal dominant 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.0

DANN

Benign

0.97

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