Variant 6-34036151-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000841.4(GRM4):c.1959G>A(p.Ser653=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,614,160 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 118 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 108 hom. )

Consequence

GRM4
NM_000841.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.98

Variant links:

Genes affected

GRM4 (HGNC:4596): (glutamate metabotropic receptor 4) 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 metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

GRM4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 6-34036151-C-T is Benign according to our data. Variant chr6-34036151-C-T is described in ClinVar as [Benign]. Clinvar id is 788533.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM4	NM_000841.4 linkuse as main transcript	c.1959G>A	p.Ser653=	synonymous_variant	9/11	ENST00000538487.7	NP_000832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM4	ENST00000538487.7 linkuse as main transcript	c.1959G>A	p.Ser653=	synonymous_variant	9/11	2	NM_000841.4	ENSP00000440556	P1	Q14833-1

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3500

AN:

152206

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0722

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00397

Gnomad OTH

AF:

0.0210

GnomAD3 exomes

AF:

0.00783

AC:

1968

AN:

251256

Hom.:

AF XY:

0.00652

AC XY:

886

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.0738

Gnomad AMR exome

AF:

0.00657

Gnomad ASJ exome

AF:

0.00903

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00340

Gnomad OTH exome

AF:

0.00653

GnomAD4 exome

AF:

0.00576

AC:

8422

AN:

1461836

Hom.:

108

Cov.:

AF XY:

0.00533

AC XY:

3878

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0703

Gnomad4 AMR exome

AF:

0.00738

Gnomad4 ASJ exome

AF:

0.00834

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000730

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00448

Gnomad4 OTH exome

AF:

0.00690

GnomAD4 genome

AF:

0.0231

AC:

3514

AN:

152324

Hom.:

118

Cov.:

AF XY:

0.0219

AC XY:

1634

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0724

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00397

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0137

Hom.:

Bravo

AF:

0.0264

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.99

DANN

Benign

0.60

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