rs2071246

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000843.4(GRM6):c.1131C>T(p.Asp377Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,610,862 control chromosomes in the GnomAD database, including 448,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41165 hom., cov: 24)

Exomes 𝑓: 0.75 ( 407601 hom. )

Consequence

GRM6
NM_000843.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -1.78

Publications

23 publications found

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:

ENSG00000254035 (HGNC:):

ENSG00000254035 links:

ZNF454 (HGNC:21200): (zinc finger protein 454) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF454 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 5-178989287-G-A is Benign according to our data. Variant chr5-178989287-G-A is described in ClinVar as Benign. ClinVar VariationId is 99625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.78 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM6	NM_000843.4 link	c.1131C>T	p.Asp377Asp	synonymous_variant	Exon 6 of 11	ENST00000517717.3	NP_000834.2
ZNF454	XR_007058600.1 link	n.5644-460G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
GRM6	ENST00000517717.3 link	c.1131C>T	p.Asp377Asp	synonymous_variant	Exon 6 of 11	5	NM_000843.4	ENSP00000430767.1
GRM6	ENST00000231188.9 link	c.1131C>T	p.Asp377Asp	synonymous_variant	Exon 5 of 10	2		ENSP00000231188.5
GRM6	ENST00000650031.1 link	c.1131C>T	p.Asp377Asp	synonymous_variant	Exon 7 of 12			ENSP00000497110.1
ENSG00000254035	ENST00000519491.1 link	n.305-460G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.740

AC:

110789

AN:

149682

Hom.:

41126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.755

Gnomad AMI

AF:

0.435

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.646

Gnomad EAS

AF:

0.707

Gnomad SAS

AF:

0.660

Gnomad FIN

AF:

0.800

Gnomad MID

AF:

0.672

Gnomad NFE

AF:

0.755

Gnomad OTH

AF:

0.713

GnomAD2 exomes

AF:

0.723

AC:

181643

AN:

251364

AF XY:

0.719

show subpopulations

Gnomad AFR exome

AF:

0.753

Gnomad AMR exome

AF:

0.668

Gnomad ASJ exome

AF:

0.641

Gnomad EAS exome

AF:

0.703

Gnomad FIN exome

AF:

0.795

Gnomad NFE exome

AF:

0.750

Gnomad OTH exome

AF:

0.726

GnomAD4 exome

AF:

0.746

AC:

1089419

AN:

1461070

Hom.:

407601

Cov.:

AF XY:

0.742

AC XY:

539050

AN XY:

726852

show subpopulations

African (AFR)

AF:

0.752

AC:

25158

AN:

33464

American (AMR)

AF:

0.674

AC:

30125

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.644

AC:

16820

AN:

26128

East Asian (EAS)

AF:

0.663

AC:

26304

AN:

39690

South Asian (SAS)

AF:

0.655

AC:

56478

AN:

86230

European-Finnish (FIN)

AF:

0.793

AC:

42363

AN:

53392

Middle Eastern (MID)

AF:

0.665

AC:

3781

AN:

5686

European-Non Finnish (NFE)

AF:

0.759

AC:

843708

AN:

1111414

Other (OTH)

AF:

0.740

AC:

44682

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

15592

31184

46775

62367

77959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20370

40740

61110

81480

101850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.740

AC:

110880

AN:

149792

Hom.:

41165

Cov.:

AF XY:

0.739

AC XY:

53917

AN XY:

72942

show subpopulations

African (AFR)

AF:

0.754

AC:

30627

AN:

40594

American (AMR)

AF:

0.676

AC:

10151

AN:

15016

Ashkenazi Jewish (ASJ)

AF:

0.646

AC:

2229

AN:

3452

East Asian (EAS)

AF:

0.706

AC:

3510

AN:

4970

South Asian (SAS)

AF:

0.660

AC:

3117

AN:

4720

European-Finnish (FIN)

AF:

0.800

AC:

8151

AN:

10192

Middle Eastern (MID)

AF:

0.656

AC:

189

AN:

288

European-Non Finnish (NFE)

AF:

0.755

AC:

51033

AN:

67588

Other (OTH)

AF:

0.715

AC:

1481

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1410

2820

4230

5640

7050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.743

Hom.:

63689

Bravo

AF:

0.731

Asia WGS

AF:

0.716

AC:

2487

AN:

3476

EpiCase

AF:

0.733

EpiControl

AF:

0.731

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 07, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2Other:1

Retina International

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital stationary night blindness 1B

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

-0.92

CADD

Benign

0.35

(source)

DANN

Benign

0.43

PhyloP100

-1.8

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over