Genetic Variant GRM7:c.1516-16915C>T (chr3-7561507-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000844.4(GRM7):c.1516-16915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 456,316 control chromosomes in the GnomAD database, including 3,098 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 0.12 ( 1229 hom., cov: 32)

Exomes 𝑓: 0.10 ( 1869 hom. )

Consequence

GRM7
NM_000844.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4 link	c.1516-16915C>T		intron_variant	Intron 7 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.1516-16915C>T		intron_variant	Intron 7 of 9	1	NM_000844.4	ENSP00000350348.4		Q14831-1
GRM7	ENST00000440923.7 link	n.1516-16915C>T		intron_variant	Intron 7 of 11	2		ENSP00000412329.3		H7C3K2

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18629

AN:

151922

Hom.:

1229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.0960

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.0684

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.0878

GnomAD3 exomes

AF:

0.0940

AC:

12618

AN:

134250

Hom.:

748

AF XY:

0.0895

AC XY:

6542

AN XY:

73122

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.0831

Gnomad ASJ exome

AF:

0.0783

Gnomad EAS exome

AF:

0.0747

Gnomad SAS exome

AF:

0.0279

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.0845

GnomAD4 exome

AF:

0.100

AC:

30421

AN:

304276

Hom.:

1869

Cov.:

AF XY:

0.0928

AC XY:

16084

AN XY:

173254

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.0814

Gnomad4 ASJ exome

AF:

0.0782

Gnomad4 EAS exome

AF:

0.0704

Gnomad4 SAS exome

AF:

0.0290

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.0982

GnomAD4 genome

AF:

0.123

AC:

18631

AN:

152040

Hom.:

1229

Cov.:

AF XY:

0.122

AC XY:

9055

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.0958

Gnomad4 ASJ

AF:

0.0674

Gnomad4 EAS

AF:

0.0684

Gnomad4 SAS

AF:

0.0255

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.128

Gnomad4 OTH

AF:

0.0883

Alfa

AF:

0.116

Hom.:

1634

Bravo

AF:

0.119

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.8

DANN

Benign

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over