chr6-146434706-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001278064.2(GRM1):c.3495C>A(p.Pro1165Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,602,804 control chromosomes in the GnomAD database, including 226,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24251 hom., cov: 33)

Exomes 𝑓: 0.53 ( 202436 hom. )

Consequence

GRM1
NM_001278064.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -7.05

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 6-146434706-C-A is Benign according to our data. Variant chr6-146434706-C-A is described in ClinVar as [Benign]. Clinvar id is 129213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-146434706-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-7.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM1	NM_001278064.2 link	c.3495C>A	p.Pro1165Pro	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.3495C>A	p.Pro1165Pro	synonymous_variant	Exon 8 of 8	1	NM_001278064.2	ENSP00000282753.1		Q13255-1

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84959

AN:

152006

Hom.:

24226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.603

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.562

GnomAD3 exomes

AF:

0.520

AC:

124677

AN:

239870

Hom.:

33324

AF XY:

0.524

AC XY:

68830

AN XY:

131308

show subpopulations

Gnomad AFR exome

AF:

0.678

Gnomad AMR exome

AF:

0.396

Gnomad ASJ exome

AF:

0.573

Gnomad EAS exome

AF:

0.515

Gnomad SAS exome

AF:

0.600

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.519

Gnomad OTH exome

AF:

0.526

GnomAD4 exome

AF:

0.526

AC:

762612

AN:

1450680

Hom.:

202436

Cov.:

AF XY:

0.528

AC XY:

381525

AN XY:

722168

show subpopulations

Gnomad4 AFR exome

AF:

0.676

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.568

Gnomad4 EAS exome

AF:

0.496

Gnomad4 SAS exome

AF:

0.600

Gnomad4 FIN exome

AF:

0.447

Gnomad4 NFE exome

AF:

0.522

Gnomad4 OTH exome

AF:

0.541

GnomAD4 genome

AF:

0.559

AC:

85025

AN:

152124

Hom.:

24251

Cov.:

AF XY:

0.555

AC XY:

41276

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.673

Gnomad4 AMR

AF:

0.491

Gnomad4 ASJ

AF:

0.565

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.604

Gnomad4 FIN

AF:

0.447

Gnomad4 NFE

AF:

0.522

Gnomad4 OTH

AF:

0.566

Alfa

AF:

0.501

Hom.:

5145

Bravo

AF:

0.563

Asia WGS

AF:

0.579

AC:

2014

AN:

3478

EpiCase

AF:

0.535

EpiControl

AF:

0.536

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 09, 2019

GeneDx

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

- -

Jul 15, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

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. -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

-0.65

CADD

Benign

0.31

DANN

Benign

0.90

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