rs780712950

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PVS1_SupportingBP6_Moderate

The NM_007327.4(GRIN1):c.1A>T(p.Met1?) variant causes a initiator codon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,587,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

GRIN1
NM_007327.4 initiator_codon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.66

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: G2P, Labcorp Genetics (formerly Invitae), 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: Ambry Genetics, G2P
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: Likely_benign. The variant received -1 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 4 codons. Genomic position: 137139496. Lost 0.004 part of the original CDS.

BP6

Variant 9-137139487-A-T is Benign according to our data. Variant chr9-137139487-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 539839.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007327.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRIN1	NM_007327.4	MANE Select	c.1A>T	p.Met1?	initiator_codon	Exon 1 of 20	NP_015566.1	Q05586-1
GRIN1	NM_001437330.1		c.1A>T	p.Met1?	initiator_codon	Exon 1 of 21	NP_001424259.1
GRIN1	NM_001185090.2		c.1A>T	p.Met1?	initiator_codon	Exon 1 of 21	NP_001172019.1	Q05586-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRIN1	ENST00000371561.8	TSL:1 MANE Select	c.1A>T	p.Met1?	initiator_codon	Exon 1 of 20	ENSP00000360616.3	Q05586-1
GRIN1	ENST00000371553.8	TSL:1	c.1A>T	p.Met1?	initiator_codon	Exon 1 of 21	ENSP00000360608.3	Q05586-6
GRIN1	ENST00000371560.5	TSL:1	c.1A>T	p.Met1?	initiator_codon	Exon 1 of 20	ENSP00000360615.3	Q05586-7

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000181

AC:

AN:

221072

AF XY:

0.0000245

show subpopulations

Gnomad AFR exome

AF:

0.000301

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000557

AC:

AN:

1435766

Hom.:

Cov.:

AF XY:

0.00000422

AC XY:

AN XY:

711536

show subpopulations

African (AFR)

AF:

0.0000908

AC:

AN:

33022

American (AMR)

AF:

0.0000229

AC:

AN:

43638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25724

East Asian (EAS)

AF:

0.00

AC:

AN:

38944

South Asian (SAS)

AF:

0.00

AC:

AN:

85074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.00000364

AC:

AN:

1099684

Other (OTH)

AF:

0.00

AC:

AN:

59296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151992

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41406

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67950

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

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:

0.00

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000166

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Uncertain

0.0

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.25

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.89

MetaRNN

Pathogenic

0.98

MetaSVM

Benign

-0.83

PhyloP100

2.7

PROVEAN

Benign

-0.91

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

Sift4G

Benign

0.15

Polyphen

0.17

Vest4

0.82

MutPred

0.95

Gain of helix (P = 0.0496)

MVP

0.96

ClinPred

0.85

GERP RS

2.9

PromoterAI

-0.038

Neutral

(source)

Varity_R

0.88

gMVP

0.83

Mutation Taster

=134/66

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over