3-7579141-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000844.4(GRM7):c.2235G>A(p.Gly745Gly) 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 1,612,422 control chromosomes in the GnomAD database, including 60,565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4792 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55773 hom. )

Consequence

GRM7
NM_000844.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.142

Publications

18 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-7579141-G-A is Benign according to our data. Variant chr3-7579141-G-A is described in ClinVar as Benign. ClinVar VariationId is 1168984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.142 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	NM_000844.4	MANE Select	c.2235G>A	p.Gly745Gly	synonymous	Exon 8 of 10	NP_000835.1
	GRM7	NM_181874.3		c.2235G>A	p.Gly745Gly	synonymous	Exon 8 of 11	NP_870989.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GRM7	ENST00000357716.9	TSL:1 MANE Select	c.2235G>A	p.Gly745Gly	synonymous	Exon 8 of 10	ENSP00000350348.4
GRM7	ENST00000389336.8	TSL:1	c.2235G>A	p.Gly745Gly	synonymous	Exon 8 of 10	ENSP00000373987.4
GRM7	ENST00000389335.7	TSL:1	n.2235G>A		non_coding_transcript_exon	Exon 8 of 11	ENSP00000373986.3

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34479

AN:

151842

Hom.:

4781

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0832

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.137

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.192

GnomAD2 exomes

AF:

0.258

AC:

64715

AN:

251158

AF XY:

0.254

show subpopulations

Gnomad AFR exome

AF:

0.0778

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.269

AC:

392259

AN:

1460462

Hom.:

55773

Cov.:

AF XY:

0.266

AC XY:

193161

AN XY:

726600

show subpopulations

African (AFR)

AF:

0.0722

AC:

2416

AN:

33454

American (AMR)

AF:

0.282

AC:

12609

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

6224

AN:

26132

East Asian (EAS)

AF:

0.159

AC:

6296

AN:

39694

South Asian (SAS)

AF:

0.179

AC:

15398

AN:

86236

European-Finnish (FIN)

AF:

0.425

AC:

22723

AN:

53418

Middle Eastern (MID)

AF:

0.126

AC:

727

AN:

5764

European-Non Finnish (NFE)

AF:

0.280

AC:

311010

AN:

1110686

Other (OTH)

AF:

0.246

AC:

14856

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

14791

29582

44373

59164

73955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10138

20276

30414

40552

50690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.227

AC:

34510

AN:

151960

Hom.:

4792

Cov.:

AF XY:

0.233

AC XY:

17337

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.0832

AC:

3450

AN:

41456

American (AMR)

AF:

0.252

AC:

3849

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

775

AN:

3468

East Asian (EAS)

AF:

0.155

AC:

795

AN:

5136

South Asian (SAS)

AF:

0.170

AC:

815

AN:

4806

European-Finnish (FIN)

AF:

0.449

AC:

4739

AN:

10564

Middle Eastern (MID)

AF:

0.140

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.285

AC:

19390

AN:

67950

Other (OTH)

AF:

0.191

AC:

403

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1306

2613

3919

5226

6532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.252

Hom.:

4019

Bravo

AF:

0.208

Asia WGS

AF:

0.173

AC:

600

AN:

3478

EpiCase

AF:

0.256

EpiControl

AF:

0.251

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

(source)

DANN

Benign

0.45

PhyloP100

0.14

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over