rs12197749

chr6-146215152-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278064.2(GRM1):c.950+55555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,092 control chromosomes in the GnomAD database, including 1,519 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 (1519 hom., cov: 32)
• Consequence: GRM1 NM_001278064.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

Genes affected

GRM1 (HGNC:4593): (glutamate metabotropic receptor 1) This gene encodes a metabotropic glutamate receptor that functions by activating phospholipase C. L-glutamate is the major excitatory neurotransmitter in the central nervous system and 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 canonical alpha isoform of the encoded protein is a disulfide-linked homodimer whose activity is mediated by a G-protein-coupled phosphatidylinositol-calcium second messenger system. This gene may be associated with many disease states, including schizophrenia, bipolar disorder, depression, and breast cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM1	NM_001278064.2	c.950+55555G>A		intron_variant		ENST00000282753.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM1	ENST00000282753.6	c.950+55555G>A		intron_variant		1	NM_001278064.2	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17815 AN: 151974 Hom.: 1519 Cov.: 32

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0423

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.117 AC: 17809 AN: 152092 Hom.: 1519 Cov.: 32 AF XY: 0.115 AC XY: 8555 AN XY: 74362

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.0843

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0420

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.100

Alfa AF: 0.151 Hom.: 1570

Bravo AF: 0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.72
Dann	Benign	0.70

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

Other links and lift over

dbSNP: rs12197749; hg19: chr6-146536288;