5-178989881-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000843.4(GRM6):c.1013-476G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 233,814 control chromosomes in the GnomAD database, including 32,592 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 20807 hom., cov: 32)

Exomes 𝑓: 0.52 ( 11785 hom. )

Consequence

GRM6
NM_000843.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.649

Publications

5 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

new If you want to explore the variant's impact on the transcript NM_000843.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM6	NM_000843.4	MANE Select	c.1013-476G>A		intron	N/A	NP_000834.2	O15303

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRM6	ENST00000517717.3	TSL:5 MANE Select	c.1013-476G>A	intron	N/A	ENSP00000430767.1	O15303
GRM6	ENST00000231188.9	TSL:2	c.1013-476G>A	intron	N/A	ENSP00000231188.5	O15303
GRM6	ENST00000650031.1		c.1013-476G>A	intron	N/A	ENSP00000497110.1	O15303

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

79027

AN:

151906

Hom.:

20780

Cov.:

show subpopulations

Gnomad AFR

AF:

0.463

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.561

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.550

Gnomad OTH

AF:

0.486

GnomAD4 exome

AF:

0.524

AC:

42837

AN:

81788

Hom.:

11785

Cov.:

AF XY:

0.512

AC XY:

21624

AN XY:

42230

show subpopulations

African (AFR)

AF:

0.449

AC:

1332

AN:

2964

American (AMR)

AF:

0.551

AC:

2266

AN:

4110

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

918

AN:

2050

East Asian (EAS)

AF:

0.572

AC:

2477

AN:

4330

South Asian (SAS)

AF:

0.433

AC:

4520

AN:

10442

European-Finnish (FIN)

AF:

0.534

AC:

1776

AN:

3324

Middle Eastern (MID)

AF:

0.389

AC:

126

AN:

324

European-Non Finnish (NFE)

AF:

0.544

AC:

27125

AN:

49878

Other (OTH)

AF:

0.526

AC:

2297

AN:

4366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

917

1834

2752

3669

4586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.520

AC:

79102

AN:

152026

Hom.:

20807

Cov.:

AF XY:

0.521

AC XY:

38734

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.463

AC:

19219

AN:

41470

American (AMR)

AF:

0.537

AC:

8208

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

1657

AN:

3472

East Asian (EAS)

AF:

0.567

AC:

2928

AN:

5160

South Asian (SAS)

AF:

0.480

AC:

2316

AN:

4828

European-Finnish (FIN)

AF:

0.561

AC:

5911

AN:

10540

Middle Eastern (MID)

AF:

0.452

AC:

132

AN:

292

European-Non Finnish (NFE)

AF:

0.550

AC:

37411

AN:

67966

Other (OTH)

AF:

0.491

AC:

1035

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1901

3803

5704

7606

9507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.539

Hom.:

7802

Bravo

AF:

0.519

Asia WGS

AF:

0.556

AC:

1934

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.1

(source)

DANN

Benign

0.56

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over