dbSNP rs1564843: GRM7:c.1516-2951G>A (chr3-7575471-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000844.4(GRM7):c.1516-2951G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,034 control chromosomes in the GnomAD database, including 5,024 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 0.24 ( 5024 hom., cov: 33)

Consequence

GRM7
NM_000844.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

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

GRM7 links:

ENSG00000270207 (HGNC:):

ENSG00000270207 links:

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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4 link	c.1516-2951G>A		intron_variant	Intron 7 of 9	ENST00000357716.9	NP_000835.1	Q14831-1B2R693Q59G95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9 link	c.1516-2951G>A		intron_variant	Intron 7 of 9	1	NM_000844.4	ENSP00000350348.4		Q14831-1
GRM7	ENST00000440923.7 link	n.1516-2951G>A		intron_variant	Intron 7 of 11	2		ENSP00000412329.3		H7C3K2

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36291

AN:

151916

Hom.:

5010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.239

AC:

36339

AN:

152034

Hom.:

5024

Cov.:

AF XY:

0.245

AC XY:

18230

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.115

AC:

4779

AN:

41498

American (AMR)

AF:

0.255

AC:

3899

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

814

AN:

3464

East Asian (EAS)

AF:

0.212

AC:

1096

AN:

5170

South Asian (SAS)

AF:

0.182

AC:

875

AN:

4814

European-Finnish (FIN)

AF:

0.446

AC:

4707

AN:

10548

Middle Eastern (MID)

AF:

0.130

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.286

AC:

19454

AN:

67958

Other (OTH)

AF:

0.201

AC:

425

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1373

2746

4120

5493

6866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.278

Hom.:

754

Bravo

AF:

0.222

Asia WGS

AF:

0.201

AC:

699

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

0.23

(source)

DANN

Benign

0.39

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(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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rs1564843

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over