Variant 3-7578695-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000844.4(GRM7):c.1789C>T(p.Leu597=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,613,472 control chromosomes in the GnomAD database, including 60,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4818 hom., cov: 32)

Exomes 𝑓: 0.27 ( 56031 hom. )

Consequence

GRM7
NM_000844.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.971

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 3-7578695-C-T is Benign according to our data. Variant chr3-7578695-C-T is described in ClinVar as [Benign]. Clinvar id is 1168983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.971 with no splicing effect.

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/exons	MANE	UniProt
GRM7	NM_000844.4 linkuse as main transcript	c.1789C>T	p.Leu597=	synonymous_variant	8/10	ENST00000357716.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM7	ENST00000357716.9 linkuse as main transcript	c.1789C>T	p.Leu597=	synonymous_variant	8/10	1	NM_000844.4	P1	Q14831-1

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34549

AN:

151912

Hom.:

4807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0833

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.257

AC:

64707

AN:

251334

Hom.:

9459

AF XY:

0.254

AC XY:

34472

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.0778

Gnomad AMR exome

AF:

0.288

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.269

AC:

393615

AN:

1461442

Hom.:

56031

Cov.:

AF XY:

0.267

AC XY:

193828

AN XY:

727018

show subpopulations

Gnomad4 AFR exome

AF:

0.0726

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.158

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.425

Gnomad4 NFE exome

AF:

0.281

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.227

AC:

34579

AN:

152030

Hom.:

4818

Cov.:

AF XY:

0.234

AC XY:

17379

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0833

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.447

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.263

Hom.:

10839

Bravo

AF:

0.208

Asia WGS

AF:

0.172

AC:

599

AN:

3478

EpiCase

AF:

0.258

EpiControl

AF:

0.252

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 26, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.9

DANN

Benign

0.75

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over