rs12489404

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000844.4(GRM7):​c.879-1487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,972 control chromosomes in the GnomAD database, including 18,743 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 18743 hom., cov: 31)

Consequence

GRM7
NM_000844.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.627

Publications

2 publications found
Variant links:
Genes affected
GRM7 (HGNC:4599): (glutamate metabotropic receptor 7) L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors that have been divided into three groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5, and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3, while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]
GRM7 Gene-Disease associations (from GenCC):
  • neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRM7NM_000844.4 linkc.879-1487C>T intron_variant Intron 3 of 9 ENST00000357716.9 NP_000835.1 Q14831-1B2R693Q59G95

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRM7ENST00000357716.9 linkc.879-1487C>T intron_variant Intron 3 of 9 1 NM_000844.4 ENSP00000350348.4 Q14831-1
GRM7ENST00000440923.7 linkn.879-1487C>T intron_variant Intron 3 of 11 2 ENSP00000412329.3 H7C3K2

Frequencies

GnomAD3 genomes
AF:
0.474
AC:
71996
AN:
151854
Hom.:
18748
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.257
Gnomad AMI
AF:
0.596
Gnomad AMR
AF:
0.413
Gnomad ASJ
AF:
0.568
Gnomad EAS
AF:
0.469
Gnomad SAS
AF:
0.513
Gnomad FIN
AF:
0.537
Gnomad MID
AF:
0.579
Gnomad NFE
AF:
0.600
Gnomad OTH
AF:
0.514
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.474
AC:
71998
AN:
151972
Hom.:
18743
Cov.:
31
AF XY:
0.471
AC XY:
34965
AN XY:
74258
show subpopulations
African (AFR)
AF:
0.257
AC:
10659
AN:
41470
American (AMR)
AF:
0.412
AC:
6292
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.568
AC:
1972
AN:
3470
East Asian (EAS)
AF:
0.469
AC:
2416
AN:
5146
South Asian (SAS)
AF:
0.512
AC:
2470
AN:
4820
European-Finnish (FIN)
AF:
0.537
AC:
5667
AN:
10554
Middle Eastern (MID)
AF:
0.554
AC:
163
AN:
294
European-Non Finnish (NFE)
AF:
0.599
AC:
40732
AN:
67946
Other (OTH)
AF:
0.516
AC:
1087
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1814
3627
5441
7254
9068
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
652
1304
1956
2608
3260
<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:
0.549
Hom.:
18672
Bravo
AF:
0.453
Asia WGS
AF:
0.513
AC:
1784
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.32
DANN
Benign
0.49
PhyloP100
-0.63
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12489404; hg19: chr3-7346698; API