dbSNP rs329037: GRM7:c.2699-18658C>A (chr3-7721699-C-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.2699-18658C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,086 control chromosomes in the GnomAD database, including 6,934 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 0.29 ( 6934 hom., cov: 33)

Consequence

GRM7
NM_000844.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0300

Publications

4 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:

ENSG00000270207 (HGNC:):

ENSG00000270207 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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4 link	c.2699-18658C>A	intron_variant	Intron 9 of 9	ENST00000357716.9	NP_000835.1	Q14831-1B2R693Q59G95
GRM7	NM_181874.3 link	c.*22-18658C>A	intron_variant	Intron 10 of 10		NP_870989.1	Q14831-2B2R693B9EGG9
GRM7	XM_017006272.2 link	c.*22-18658C>A	intron_variant	Intron 10 of 10		XP_016861761.1
GRM7	XM_017006273.2 link	c.2201-18658C>A	intron_variant	Intron 9 of 9		XP_016861762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9 link	c.2699-18658C>A		intron_variant	Intron 9 of 9	1	NM_000844.4	ENSP00000350348.4		Q14831-1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44662

AN:

151966

Hom.:

6925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.340

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

GnomAD4 genome

AF:

0.294

AC:

44696

AN:

152086

Hom.:

6934

Cov.:

AF XY:

0.288

AC XY:

21382

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.224

AC:

9307

AN:

41492

American (AMR)

AF:

0.293

AC:

4474

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1346

AN:

3462

East Asian (EAS)

AF:

0.159

AC:

824

AN:

5186

South Asian (SAS)

AF:

0.330

AC:

1585

AN:

4806

European-Finnish (FIN)

AF:

0.222

AC:

2346

AN:

10576

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23650

AN:

67964

Other (OTH)

AF:

0.336

AC:

711

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1593

3187

4780

6374

7967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.336

Hom.:

14874

Bravo

AF:

0.293

Asia WGS

AF:

0.274

AC:

951

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.83

(source)

DANN

Benign

0.30

PhyloP100

0.030

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