3-7464418-A-G

Variant summary

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

The NM_000844.4(GRM7):​c.1515+2696A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,164 control chromosomes in the GnomAD database, including 2,436 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 0.18 ( 2436 hom., cov: 31)

Consequence

GRM7
NM_000844.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.192
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]

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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=-0.8).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRM7NM_000844.4 linkuse as main transcriptc.1515+2696A>G intron_variant ENST00000357716.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRM7ENST00000357716.9 linkuse as main transcriptc.1515+2696A>G intron_variant 1 NM_000844.4 P1Q14831-1

Frequencies

GnomAD3 genomes
AF:
0.175
AC:
26630
AN:
152046
Hom.:
2431
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.147
Gnomad AMI
AF:
0.201
Gnomad AMR
AF:
0.172
Gnomad ASJ
AF:
0.226
Gnomad EAS
AF:
0.117
Gnomad SAS
AF:
0.370
Gnomad FIN
AF:
0.189
Gnomad MID
AF:
0.212
Gnomad NFE
AF:
0.179
Gnomad OTH
AF:
0.167
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.175
AC:
26673
AN:
152164
Hom.:
2436
Cov.:
31
AF XY:
0.177
AC XY:
13203
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.147
Gnomad4 AMR
AF:
0.172
Gnomad4 ASJ
AF:
0.226
Gnomad4 EAS
AF:
0.118
Gnomad4 SAS
AF:
0.371
Gnomad4 FIN
AF:
0.189
Gnomad4 NFE
AF:
0.179
Gnomad4 OTH
AF:
0.174
Alfa
AF:
0.175
Hom.:
775
Bravo
AF:
0.164
Asia WGS
AF:
0.292
AC:
1016
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
6.3
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: rs1450092; hg19: chr3-7506105; API