dbSNP rs6782718: GRM7:c.1175-6518G>A (chr3-7446089-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.1175-6518G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,996 control chromosomes in the GnomAD database, including 10,996 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 0.35 ( 10996 hom., cov: 32)

Consequence

GRM7
NM_000844.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0710

Publications

1 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=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4 link	c.1175-6518G>A		intron_variant	Intron 5 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.1175-6518G>A		intron_variant	Intron 5 of 9	1	NM_000844.4	ENSP00000350348.4		Q14831-1
GRM7	ENST00000440923.7 link	n.1175-6518G>A		intron_variant	Intron 5 of 11	2		ENSP00000412329.3		H7C3K2

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53911

AN:

151880

Hom.:

10987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.0980

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.382

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

GnomAD4 genome

AF:

0.355

AC:

53932

AN:

151996

Hom.:

10996

Cov.:

AF XY:

0.350

AC XY:

25983

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.187

AC:

7750

AN:

41464

American (AMR)

AF:

0.308

AC:

4708

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1185

AN:

3468

East Asian (EAS)

AF:

0.0977

AC:

505

AN:

5170

South Asian (SAS)

AF:

0.208

AC:

1001

AN:

4816

European-Finnish (FIN)

AF:

0.464

AC:

4893

AN:

10536

Middle Eastern (MID)

AF:

0.380

AC:

111

AN:

292

European-Non Finnish (NFE)

AF:

0.479

AC:

32575

AN:

67974

Other (OTH)

AF:

0.386

AC:

811

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1645

3289

4934

6578

8223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.427

Hom.:

7482

Bravo

AF:

0.341

Asia WGS

AF:

0.184

AC:

640

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.7

(source)

DANN

Benign

0.15

PhyloP100

0.071

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over