Genetic Variant GRM7:c.519+106487C>T (chr3-6968394-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000844.4(GRM7):c.519+106487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,960 control chromosomes in the GnomAD database, including 4,484 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 0.22 ( 4484 hom., cov: 32)

Consequence

GRM7
NM_000844.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0350

Publications

5 publications found

Variant links:

Genes affected

GRM7 (HGNC:4599): (glutamate metabotropic receptor 7) L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it 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 three 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

GRM7 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

GRM7 links:

Genome browser will be placed here

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 = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4 link	c.519+106487C>T		intron_variant	Intron 1 of 9	ENST00000357716.9	NP_000835.1	Q14831-1B2R693Q59G95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9 link	c.519+106487C>T		intron_variant	Intron 1 of 9	1	NM_000844.4	ENSP00000350348.4		Q14831-1
GRM7	ENST00000440923.7 link	n.519+106487C>T		intron_variant	Intron 1 of 11	2		ENSP00000412329.3		H7C3K2

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

33012

AN:

151840

Hom.:

4476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.617

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.210

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.217

AC:

33036

AN:

151960

Hom.:

4484

Cov.:

AF XY:

0.228

AC XY:

16935

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.112

AC:

4645

AN:

41458

American (AMR)

AF:

0.285

AC:

4358

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

653

AN:

3472

East Asian (EAS)

AF:

0.617

AC:

3171

AN:

5136

South Asian (SAS)

AF:

0.435

AC:

2089

AN:

4804

European-Finnish (FIN)

AF:

0.308

AC:

3247

AN:

10558

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14094

AN:

67956

Other (OTH)

AF:

0.214

AC:

450

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1257

2514

3770

5027

6284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.211

Hom.:

6931

Bravo

AF:

0.208

Asia WGS

AF:

0.501

AC:

1736

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.9

(source)

DANN

Benign

0.79

PhyloP100

0.035

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over