rs3749380

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.222C>T(p.Asn74Asn) 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

Publications

41 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

GRM7 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=-0.44).

BP6

Variant 3-6861610-C-T is Benign according to our data. Variant chr3-6861610-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	NM_000844.4	MANE Select	c.222C>T	p.Asn74Asn	synonymous	Exon 1 of 10	NP_000835.1	Q14831-1
	GRM7	NM_181874.3		c.222C>T	p.Asn74Asn	synonymous	Exon 1 of 11	NP_870989.1	Q14831-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRM7	ENST00000357716.9	TSL:1 MANE Select	c.222C>T	p.Asn74Asn	synonymous	Exon 1 of 10	ENSP00000350348.4	Q14831-1
GRM7	ENST00000389336.8	TSL:1	c.222C>T	p.Asn74Asn	synonymous	Exon 1 of 10	ENSP00000373987.4	Q14831-5
GRM7	ENST00000389335.7	TSL:1	n.222C>T		non_coding_transcript_exon	Exon 1 of 11	ENSP00000373986.3	Q14831-4

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

GnomAD2 exomes

AF:

0.400

AC:

98027

AN:

244934

AF XY:

0.409

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 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

African (AFR)

AF:

0.333

AC:

11130

AN:

33410

American (AMR)

AF:

0.405

AC:

17966

AN:

44336

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

10589

AN:

26078

East Asian (EAS)

AF:

0.317

AC:

12550

AN:

39564

South Asian (SAS)

AF:

0.559

AC:

48029

AN:

85978

European-Finnish (FIN)

AF:

0.369

AC:

19513

AN:

52904

Middle Eastern (MID)

AF:

0.446

AC:

2571

AN:

5764

European-Non Finnish (NFE)

AF:

0.391

AC:

434566

AN:

1110212

Other (OTH)

AF:

0.399

AC:

24047

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

18859

37717

56576

75434

94293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13668

27336

41004

54672

68340

<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:

0.373

AC:

56650

AN:

151964

Hom.:

10734

Cov.:

AF XY:

0.376

AC XY:

27943

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.329

AC:

13642

AN:

41486

American (AMR)

AF:

0.397

AC:

6068

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

1374

AN:

3470

East Asian (EAS)

AF:

0.304

AC:

1542

AN:

5074

South Asian (SAS)

AF:

0.557

AC:

2687

AN:

4820

European-Finnish (FIN)

AF:

0.361

AC:

3815

AN:

10574

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.388

AC:

26381

AN:

67944

Other (OTH)

AF:

0.393

AC:

829

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1804

3608

5411

7215

9019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.386

Hom.:

21193

Bravo

AF:

0.368

Asia WGS

AF:

0.425

AC:

1476

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

GRM7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

9.5

(source)

DANN

Benign

0.94

PhyloP100

0.47

PromoterAI

0.0026

Neutral

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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

Computational scores

Splicing

Publications

Other links and lift over