rs2189816

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000840.3(GRM3):​c.-140-52876T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 152,094 control chromosomes in the GnomAD database, including 962 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 0.099 ( 962 hom., cov: 32)

Consequence

GRM3
NM_000840.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.464
Variant links:
Genes affected
GRM3 (HGNC:4595): (glutamate metabotropic receptor 3) L-glutamate is the major excitatory neurotransmitter in the central nervous system and 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 3 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. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRM3NM_000840.3 linkuse as main transcriptc.-140-52876T>C intron_variant ENST00000361669.7
GRM3NM_001363522.2 linkuse as main transcriptc.-140-52876T>C intron_variant
GRM3XM_017012073.3 linkuse as main transcriptc.-140-52876T>C intron_variant
GRM3XM_047420268.1 linkuse as main transcriptc.-140-52876T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRM3ENST00000361669.7 linkuse as main transcriptc.-140-52876T>C intron_variant 1 NM_000840.3 P1Q14832-1

Frequencies

GnomAD3 genomes
AF:
0.0989
AC:
15026
AN:
151976
Hom.:
962
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0263
Gnomad AMI
AF:
0.0384
Gnomad AMR
AF:
0.0940
Gnomad ASJ
AF:
0.102
Gnomad EAS
AF:
0.00174
Gnomad SAS
AF:
0.107
Gnomad FIN
AF:
0.120
Gnomad MID
AF:
0.104
Gnomad NFE
AF:
0.148
Gnomad OTH
AF:
0.107
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0987
AC:
15017
AN:
152094
Hom.:
962
Cov.:
32
AF XY:
0.0965
AC XY:
7174
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.0262
Gnomad4 AMR
AF:
0.0938
Gnomad4 ASJ
AF:
0.102
Gnomad4 EAS
AF:
0.00175
Gnomad4 SAS
AF:
0.107
Gnomad4 FIN
AF:
0.120
Gnomad4 NFE
AF:
0.148
Gnomad4 OTH
AF:
0.106
Alfa
AF:
0.129
Hom.:
744
Bravo
AF:
0.0937
Asia WGS
AF:
0.0410
AC:
145
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.7
DANN
Benign
0.84

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.

Other links and lift over

dbSNP: rs2189816; hg19: chr7-86341446; API