Variant 6-34022848-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_000841.4(GRM4):c.2712C>T(p.Tyr904=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 1,613,898 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 35 hom. )

Consequence

GRM4
NM_000841.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 6-34022848-G-A is Benign according to our data. Variant chr6-34022848-G-A is described in ClinVar as [Benign]. Clinvar id is 787826.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.14 with no splicing effect.

BS2

High AC in GnomAd4 at 706 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM4	NM_000841.4 linkuse as main transcript	c.2712C>T	p.Tyr904=	synonymous_variant	11/11	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.2712C>T	p.Tyr904=	synonymous_variant	11/11	2	NM_000841.4	ENSP00000440556	P1	Q14833-1

Frequencies

GnomAD3 genomes

AF:

0.00463

AC:

705

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00875

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00647

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00562

AC:

1404

AN:

249774

Hom.:

AF XY:

0.00548

AC XY:

740

AN XY:

135150

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00558

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.00169

Gnomad SAS exome

AF:

0.00265

Gnomad FIN exome

AF:

0.00915

Gnomad NFE exome

AF:

0.00653

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

AF:

0.00632

AC:

9240

AN:

1461538

Hom.:

Cov.:

AF XY:

0.00627

AC XY:

4557

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00539

Gnomad4 ASJ exome

AF:

0.00991

Gnomad4 EAS exome

AF:

0.00111

Gnomad4 SAS exome

AF:

0.00310

Gnomad4 FIN exome

AF:

0.00890

Gnomad4 NFE exome

AF:

0.00679

Gnomad4 OTH exome

AF:

0.00603

GnomAD4 genome

AF:

0.00463

AC:

706

AN:

152360

Hom.:

Cov.:

AF XY:

0.00478

AC XY:

356

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00875

Gnomad4 NFE

AF:

0.00647

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00541

Hom.:

Bravo

AF:

0.00431

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00717

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

-0.39

CADD

Benign

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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