Genetic Variant GRM7:c.737-50327G>A (chr3-7248357-G-A) – 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.737-50327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,176 control chromosomes in the GnomAD database, including 61,778 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 0.90 ( 61778 hom., cov: 32)

Consequence

GRM7
NM_000844.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.105

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:

ENSG00000288030 (HGNC:):

ENSG00000288030 links:

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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=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4 link	c.737-50327G>A		intron_variant	Intron 2 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.737-50327G>A		intron_variant	Intron 2 of 9	1	NM_000844.4	ENSP00000350348.4		Q14831-1
GRM7	ENST00000440923.7 link	n.737-50327G>A		intron_variant	Intron 2 of 11	2		ENSP00000412329.3		H7C3K2

Frequencies

GnomAD3 genomes

AF:

0.899

AC:

136709

AN:

152058

Hom.:

61711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.972

Gnomad AMI

AF:

0.870

Gnomad AMR

AF:

0.939

Gnomad ASJ

AF:

0.938

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.887

Gnomad FIN

AF:

0.862

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.844

Gnomad OTH

AF:

0.922

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

GnomAD4 genome

AF:

0.899

AC:

136837

AN:

152176

Hom.:

61778

Cov.:

AF XY:

0.903

AC XY:

67164

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.972

AC:

40395

AN:

41554

American (AMR)

AF:

0.940

AC:

14347

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.938

AC:

3257

AN:

3472

East Asian (EAS)

AF:

0.979

AC:

5064

AN:

5170

South Asian (SAS)

AF:

0.887

AC:

4274

AN:

4816

European-Finnish (FIN)

AF:

0.862

AC:

9124

AN:

10590

Middle Eastern (MID)

AF:

0.929

AC:

273

AN:

294

European-Non Finnish (NFE)

AF:

0.844

AC:

57359

AN:

67986

Other (OTH)

AF:

0.924

AC:

1951

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

698

1395

2093

2790

3488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<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:

0.876

Hom.:

9891

Bravo

AF:

0.912

Asia WGS

AF:

0.940

AC:

3265

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.8

(source)

DANN

Benign

0.61

PhyloP100

0.10

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