Variant 7-126446381-A-AG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_000845.3(GRM8):c.2431-10_2431-9insC variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000999 in 1,564,058 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 2 hom. )

Consequence

GRM8
NM_000845.3 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0410

Variant links:

Genes affected

GRM8 (HGNC:4600): (glutamate metabotropic receptor 8) 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. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

GRM8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 7-126446381-A-AG is Benign according to our data. Variant chr7-126446381-A-AG is described in ClinVar as [Benign]. Clinvar id is 3044373.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM8	NM_000845.3 linkuse as main transcript	c.2431-10_2431-9insC		splice_polypyrimidine_tract_variant, intron_variant		ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7 linkuse as main transcript	c.2431-10_2431-9insC		splice_polypyrimidine_tract_variant, intron_variant		5	NM_000845.3	ENSP00000344173	P1	O00222-1

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

154

AN:

149726

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00337

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00624

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000722

Gnomad OTH

AF:

0.00193

GnomAD3 exomes

AF:

0.00150

AC:

340

AN:

227346

Hom.:

AF XY:

0.00194

AC XY:

240

AN XY:

123654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000735

Gnomad ASJ exome

AF:

0.00118

Gnomad EAS exome

AF:

0.0000592

Gnomad SAS exome

AF:

0.00727

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000989

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.000996

AC:

1408

AN:

1414222

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

871

AN XY:

702966

show subpopulations

Gnomad4 AFR exome

AF:

0.0000641

Gnomad4 AMR exome

AF:

0.00102

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00773

Gnomad4 FIN exome

AF:

0.0000382

Gnomad4 NFE exome

AF:

0.000499

Gnomad4 OTH exome

AF:

0.00170

GnomAD4 genome

AF:

0.00103

AC:

155

AN:

149836

Hom.:

Cov.:

AF XY:

0.000929

AC XY:

AN XY:

73190

show subpopulations

Gnomad4 AFR

AF:

0.000226

Gnomad4 AMR

AF:

0.00337

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00625

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000723

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.000370

Hom.:

Bravo

AF:

0.00137

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GRM8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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