Genetic Variant GRM7:c.-180+3183C>T (chr3-6773301-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000448328.6(GRM7):c.-180+3183C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,399,068 control chromosomes in the GnomAD database, including 134,727 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 0.40 ( 13467 hom., cov: 31)

Exomes 𝑓: 0.44 ( 121260 hom. )

Consequence

GRM7
ENST00000448328.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.631

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:

MRPS36P1 (HGNC:29771): (mitochondrial ribosomal protein S36 pseudogene 1)

MRPS36P1 links:

GRM7-AS3 (HGNC:42444): (GRM7 antisense RNA 3)

GRM7-AS3 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=-0.64).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MRPS36P1		n.6773301C>T	intragenic_variant
GRM7-AS3	NR_110123.1 link	n.150+17752G>A	intron_variant	Intron 2 of 3
GRM7-AS3	NR_110125.1 link	n.150+17752G>A	intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
GRM7	ENST00000448328.6 link	c.-180+3183C>T	intron_variant	Intron 1 of 4	4	ENSP00000393799.2	C9JU97
MRPS36P1	ENST00000421291.1 link	n.43G>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
GRM7-AS3	ENST00000412629.6 link	n.180+17752G>A	intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61062

AN:

151836

Hom.:

13469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.596

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.583

Gnomad NFE

AF:

0.476

Gnomad OTH

AF:

0.447

GnomAD4 exome

AF:

0.436

AC:

543971

AN:

1247112

Hom.:

121260

Cov.:

AF XY:

0.439

AC XY:

277073

AN XY:

630642

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.417

Gnomad4 ASJ exome

AF:

0.471

Gnomad4 EAS exome

AF:

0.616

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.439

Gnomad4 NFE exome

AF:

0.439

Gnomad4 OTH exome

AF:

0.436

GnomAD4 genome

AF:

0.402

AC:

61072

AN:

151956

Hom.:

13467

Cov.:

AF XY:

0.404

AC XY:

29994

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.459

Gnomad4 ASJ

AF:

0.474

Gnomad4 EAS

AF:

0.597

Gnomad4 SAS

AF:

0.414

Gnomad4 FIN

AF:

0.431

Gnomad4 NFE

AF:

0.476

Gnomad4 OTH

AF:

0.443

Alfa

AF:

0.412

Hom.:

2507

Bravo

AF:

0.393

Asia WGS

AF:

0.497

AC:

1729

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.65

Splicing

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