Variant chr5-178983150-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000843.4(GRM6):c.2196G>A(p.Thr732=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,613,502 control chromosomes in the GnomAD database, including 26,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2846 hom., cov: 33)

Exomes 𝑓: 0.17 ( 23527 hom. )

Consequence

GRM6
NM_000843.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -5.84

Variant links:

Genes affected

GRM6 (HGNC:4598): (glutamate metabotropic receptor 6) 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. Mutations in this gene result in congenital stationary night blindness type 1B. [provided by RefSeq, May 2018]

GRM6 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 5-178983150-C-T is Benign according to our data. Variant chr5-178983150-C-T is described in ClinVar as [Benign]. Clinvar id is 99643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-178983150-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM6	NM_000843.4 linkuse as main transcript	c.2196G>A	p.Thr732=	synonymous_variant	10/11	ENST00000517717.3	NP_000834.2
ZNF454	XR_007058600.1 linkuse as main transcript	n.5644-6597C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM6	ENST00000517717.3 linkuse as main transcript	c.2196G>A	p.Thr732=	synonymous_variant	10/11	5	NM_000843.4	ENSP00000430767	P1
	ENST00000519491.1 linkuse as main transcript	n.305-6597C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28558

AN:

152022

Hom.:

2841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.203

GnomAD3 exomes

AF:

0.202

AC:

50710

AN:

251112

Hom.:

5714

AF XY:

0.205

AC XY:

27799

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.375

Gnomad SAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.172

AC:

251063

AN:

1461362

Hom.:

23527

Cov.:

AF XY:

0.175

AC XY:

127512

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.159

Gnomad4 EAS exome

AF:

0.396

Gnomad4 SAS exome

AF:

0.279

Gnomad4 FIN exome

AF:

0.175

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.188

AC:

28598

AN:

152140

Hom.:

2846

Cov.:

AF XY:

0.192

AC XY:

14252

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.187

Gnomad4 ASJ

AF:

0.167

Gnomad4 EAS

AF:

0.380

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.158

Gnomad4 OTH

AF:

0.208

Alfa

AF:

0.166

Hom.:

2715

Bravo

AF:

0.188

Asia WGS

AF:

0.334

AC:

1158

AN:

3478

EpiCase

AF:

0.167

EpiControl

AF:

0.168

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

not provided, no classification provided	literature only	Retina International	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Congenital stationary night blindness 1B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.043

DANN

Benign

0.88

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