Variant 3-6861610-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.222C>T(p.Asn74=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,610,478 control chromosomes in the GnomAD database, including 127,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10734 hom., cov: 32)

Exomes 𝑓: 0.40 ( 117180 hom. )

Consequence

GRM7
NM_000844.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.466

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=-0.44).

BP6

Variant 3-6861610-C-T is Benign according to our data. Variant chr3-6861610-C-T is described in ClinVar as [Benign]. Clinvar id is 1164859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.466 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 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.222C>T	p.Asn74=	synonymous_variant	1/10	ENST00000357716.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM7	ENST00000357716.9 linkuse as main transcript	c.222C>T	p.Asn74=	synonymous_variant	1/10	1	NM_000844.4	P1	Q14831-1

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56621

AN:

151846

Hom.:

10726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.398

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.558

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.391

GnomAD3 exomes

AF:

0.400

AC:

98027

AN:

244934

Hom.:

20105

AF XY:

0.409

AC XY:

54348

AN XY:

132730

show subpopulations

Gnomad AFR exome

AF:

0.331

Gnomad AMR exome

AF:

0.405

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.563

Gnomad FIN exome

AF:

0.366

Gnomad NFE exome

AF:

0.388

Gnomad OTH exome

AF:

0.402

GnomAD4 exome

AF:

0.398

AC:

580961

AN:

1458514

Hom.:

117180

Cov.:

AF XY:

0.404

AC XY:

292649

AN XY:

725220

show subpopulations

Gnomad4 AFR exome

AF:

0.333

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.406

Gnomad4 EAS exome

AF:

0.317

Gnomad4 SAS exome

AF:

0.559

Gnomad4 FIN exome

AF:

0.369

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.399

GnomAD4 genome

AF:

0.373

AC:

56650

AN:

151964

Hom.:

10734

Cov.:

AF XY:

0.376

AC XY:

27943

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.329

Gnomad4 AMR

AF:

0.397

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.557

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.388

Gnomad4 OTH

AF:

0.393

Alfa

AF:

0.387

Hom.:

16013

Bravo

AF:

0.368

Asia WGS

AF:

0.425

AC:

1476

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

GRM7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

9.5

DANN

Benign

0.94

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