rs7614915

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000844.4(GRM7):c.1789C>T(p.Leu597Leu) 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

Publications

15 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 -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 VariationId 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 rank	MANE	Protein	UniProt
GRM7	NM_000844.4 link	c.1789C>T	p.Leu597Leu	synonymous_variant	Exon 8 of 10	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.1789C>T	p.Leu597Leu	synonymous_variant	Exon 8 of 10	1	NM_000844.4	ENSP00000350348.4		Q14831-1
GRM7	ENST00000440923.7 link	n.1789C>T		non_coding_transcript_exon_variant	Exon 8 of 12	2		ENSP00000412329.3		H7C3K2

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

GnomAD2 exomes

AF:

0.257

AC:

64707

AN:

251334

AF XY:

0.254

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 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

African (AFR)

AF:

0.0726

AC:

2431

AN:

33476

American (AMR)

AF:

0.279

AC:

12498

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

6224

AN:

26136

East Asian (EAS)

AF:

0.158

AC:

6286

AN:

39698

South Asian (SAS)

AF:

0.179

AC:

15404

AN:

86250

European-Finnish (FIN)

AF:

0.425

AC:

22721

AN:

53412

Middle Eastern (MID)

AF:

0.127

AC:

730

AN:

5766

European-Non Finnish (NFE)

AF:

0.281

AC:

312435

AN:

1111596

Other (OTH)

AF:

0.247

AC:

14886

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16172

32344

48516

64688

80860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10186

20372

30558

40744

50930

<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:

34579

AN:

152030

Hom.:

4818

Cov.:

AF XY:

0.234

AC XY:

17379

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.0833

AC:

3455

AN:

41490

American (AMR)

AF:

0.254

AC:

3883

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

777

AN:

3468

East Asian (EAS)

AF:

0.155

AC:

796

AN:

5140

South Asian (SAS)

AF:

0.169

AC:

815

AN:

4824

European-Finnish (FIN)

AF:

0.447

AC:

4718

AN:

10556

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.286

AC:

19443

AN:

67948

Other (OTH)

AF:

0.191

AC:

402

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1283

2567

3850

5134

6417

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:

0.260

Hom.:

14953

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 26, 2021

GeneDx

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.9

(source)

DANN

Benign

0.75

PhyloP100

0.97

Mutation Taster

=99/1

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over