rs2067011

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BA1

The NM_000843.4(GRM6):c.1353T>C(p.Asn451Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,609,530 control chromosomes in the GnomAD database, including 239,795 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 19954 hom., cov: 32)

Exomes 𝑓: 0.55 ( 219841 hom. )

Consequence

GRM6
NM_000843.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0001885

Clinical Significance

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

Conservation

PhyloP100: -1.06

Publications

28 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.227).

BP6

Variant 5-178988936-A-G is Benign according to our data. Variant chr5-178988936-A-G is described in ClinVar as Benign. ClinVar VariationId is 99627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM6	NM_000843.4 link	c.1353T>C	p.Asn451Asn	splice_region_variant, synonymous_variant	Exon 7 of 11	ENST00000517717.3	NP_000834.2	O15303
ZNF454	XR_007058600.1 link	n.5644-811A>G		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM6	ENST00000517717.3 link	c.1353T>C	p.Asn451Asn	splice_region_variant, synonymous_variant	Exon 7 of 11	5	NM_000843.4	ENSP00000430767.1		O15303

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

76999

AN:

151864

Hom.:

19925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.484

Gnomad EAS

AF:

0.571

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.478

GnomAD2 exomes

AF:

0.532

AC:

130866

AN:

246060

AF XY:

0.526

show subpopulations

Gnomad AFR exome

AF:

0.406

Gnomad AMR exome

AF:

0.572

Gnomad ASJ exome

AF:

0.483

Gnomad EAS exome

AF:

0.584

Gnomad FIN exome

AF:

0.566

Gnomad NFE exome

AF:

0.546

Gnomad OTH exome

AF:

0.528

GnomAD4 exome

AF:

0.547

AC:

797723

AN:

1457548

Hom.:

219841

Cov.:

AF XY:

0.543

AC XY:

393665

AN XY:

725056

show subpopulations

African (AFR)

AF:

0.405

AC:

13541

AN:

33400

American (AMR)

AF:

0.569

AC:

25351

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

12564

AN:

26082

East Asian (EAS)

AF:

0.553

AC:

21935

AN:

39650

South Asian (SAS)

AF:

0.462

AC:

39680

AN:

85970

European-Finnish (FIN)

AF:

0.569

AC:

30320

AN:

53240

Middle Eastern (MID)

AF:

0.421

AC:

2080

AN:

4944

European-Non Finnish (NFE)

AF:

0.559

AC:

620043

AN:

1109546

Other (OTH)

AF:

0.535

AC:

32209

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

17271

34541

51812

69082

86353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17404

34808

52212

69616

87020

<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:

0.507

AC:

77071

AN:

151982

Hom.:

19954

Cov.:

AF XY:

0.509

AC XY:

37825

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.412

AC:

17071

AN:

41470

American (AMR)

AF:

0.531

AC:

8111

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.484

AC:

1679

AN:

3470

East Asian (EAS)

AF:

0.570

AC:

2925

AN:

5128

South Asian (SAS)

AF:

0.481

AC:

2320

AN:

4820

European-Finnish (FIN)

AF:

0.567

AC:

5995

AN:

10566

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.553

AC:

37533

AN:

67928

Other (OTH)

AF:

0.483

AC:

1018

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1957

3914

5872

7829

9786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.536

Hom.:

96817

Bravo

AF:

0.501

Asia WGS

AF:

0.561

AC:

1950

AN:

3478

EpiCase

AF:

0.529

EpiControl

AF:

0.519

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

- -

Nov 23, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

not provided

Benign:2Other:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retina International

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

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

-0.47

CADD

Benign

2.2

(source)

DANN

Benign

0.80

PhyloP100

-1.1

Mutation Taster

=71/29

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.014

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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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