rs2942

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_001278064.2(GRM1):c.2793G>A(p.Lys931Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,613,152 control chromosomes in the GnomAD database, including 218,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19385 hom., cov: 32)

Exomes 𝑓: 0.52 ( 198681 hom. )

Consequence

GRM1
NM_001278064.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.44

Publications

35 publications found

Variant links:

Genes affected

GRM1 (HGNC:4593): (glutamate metabotropic receptor 1) This gene encodes a metabotropic glutamate receptor that functions by activating phospholipase C. L-glutamate is the major excitatory neurotransmitter in the central nervous system and 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 canonical alpha isoform of the encoded protein is a disulfide-linked homodimer whose activity is mediated by a G-protein-coupled phosphatidylinositol-calcium second messenger system. This gene may be associated with many disease states, including schizophrenia, bipolar disorder, depression, and breast cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

GRM1 Gene-Disease associations (from GenCC):

spinocerebellar ataxia 44
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive spinocerebellar ataxia 13
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

GRM1 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=-0.46).

BP6

Variant 6-146434004-G-A is Benign according to our data. Variant chr6-146434004-G-A is described in ClinVar as Benign. ClinVar VariationId is 129209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM1	NM_001278064.2 link	c.2793G>A	p.Lys931Lys	synonymous_variant	Exon 8 of 8	ENST00000282753.6	NP_001264993.1	Q13255-1Q59HC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM1	ENST00000282753.6 link	c.2793G>A	p.Lys931Lys	synonymous_variant	Exon 8 of 8	1	NM_001278064.2	ENSP00000282753.1		Q13255-1

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76545

AN:

151844

Hom.:

19359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.472

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.600

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.522

Gnomad OTH

AF:

0.512

GnomAD2 exomes

AF:

0.504

AC:

126597

AN:

251376

AF XY:

0.512

show subpopulations

Gnomad AFR exome

AF:

0.491

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.572

Gnomad EAS exome

AF:

0.509

Gnomad FIN exome

AF:

0.448

Gnomad NFE exome

AF:

0.518

Gnomad OTH exome

AF:

0.519

GnomAD4 exome

AF:

0.519

AC:

758842

AN:

1461188

Hom.:

198681

Cov.:

AF XY:

0.523

AC XY:

380004

AN XY:

726938

show subpopulations

African (AFR)

AF:

0.487

AC:

16315

AN:

33470

American (AMR)

AF:

0.392

AC:

17532

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

14797

AN:

26122

East Asian (EAS)

AF:

0.494

AC:

19607

AN:

39698

South Asian (SAS)

AF:

0.599

AC:

51684

AN:

86240

European-Finnish (FIN)

AF:

0.449

AC:

23972

AN:

53372

Middle Eastern (MID)

AF:

0.559

AC:

3227

AN:

5768

European-Non Finnish (NFE)

AF:

0.522

AC:

579826

AN:

1111424

Other (OTH)

AF:

0.528

AC:

31882

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

23304

46609

69913

93218

116522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16636

33272

49908

66544

83180

<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:

0.504

AC:

76608

AN:

151964

Hom.:

19385

Cov.:

AF XY:

0.502

AC XY:

37242

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.485

AC:

20120

AN:

41466

American (AMR)

AF:

0.469

AC:

7160

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1954

AN:

3468

East Asian (EAS)

AF:

0.516

AC:

2650

AN:

5132

South Asian (SAS)

AF:

0.601

AC:

2894

AN:

4812

European-Finnish (FIN)

AF:

0.449

AC:

4736

AN:

10554

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.522

AC:

35436

AN:

67940

Other (OTH)

AF:

0.516

AC:

1089

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1946

3892

5838

7784

9730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.521

Hom.:

74791

Bravo

AF:

0.500

Asia WGS

AF:

0.566

AC:

1971

AN:

3478

EpiCase

AF:

0.534

EpiControl

AF:

0.535

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 15, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 25, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Autosomal recessive spinocerebellar ataxia 13

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spinocerebellar ataxia 44

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.3

(source)

DANN

Benign

0.60

PhyloP100

1.4

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over