rs202160831

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007327.4(GRIN1):c.258+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,597,266 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 2 hom. )

Consequence

GRIN1
NM_007327.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.631

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 9-137139762-C-T is Benign according to our data. Variant chr9-137139762-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 384370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00127 (193/152236) while in subpopulation NFE AF = 0.00175 (119/68014). AF 95% confidence interval is 0.00149. There are 0 homozygotes in GnomAd4. There are 93 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN1	NM_007327.4 link	c.258+18C>T		intron_variant	Intron 1 of 19	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.258+18C>T		intron_variant	Intron 1 of 19	1	NM_007327.4	ENSP00000360616.3		Q05586-1

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

193

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00175

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.00144

AC:

356

AN:

247846

AF XY:

0.00150

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.000926

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00394

Gnomad NFE exome

AF:

0.00178

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.00170

AC:

2450

AN:

1445030

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1227

AN XY:

719678

show subpopulations

African (AFR)

AF:

0.000271

AC:

AN:

33188

American (AMR)

AF:

0.00101

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26044

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39606

South Asian (SAS)

AF:

0.000978

AC:

AN:

85922

European-Finnish (FIN)

AF:

0.00395

AC:

209

AN:

52854

Middle Eastern (MID)

AF:

0.00174

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00184

AC:

2020

AN:

1097138

Other (OTH)

AF:

0.00119

AC:

AN:

59834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

125

250

374

499

624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.00127

AC:

193

AN:

152236

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41534

American (AMR)

AF:

0.000196

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00104

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00480

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00175

AC:

119

AN:

68014

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00151

Hom.:

Bravo

AF:

0.000880

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 20, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 11, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Oct 17, 2017

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.4

(source)

DANN

Benign

0.91

PhyloP100

0.63

PromoterAI

0.0074

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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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