rs2300622

Positions:

• chr6-146404307-T-C

Variant summary

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

The NM_001278064.2(GRM1):​c.2660+4608T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 152,134 control chromosomes in the GnomAD database, including 920 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 0.064 (920 hom., cov: 32)
• Consequence: GRM1 NM_001278064.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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 (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM1	NM_001278064.2	c.2660+4608T>C		intron_variant		ENST00000282753.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM1	ENST00000282753.6	c.2660+4608T>C		intron_variant		1	NM_001278064.2	P1

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9695 AN: 152016 Hom.: 920 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.0785

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.0497

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

GnomAD4 genome AF: 0.0639 AC: 9720 AN: 152134 Hom.: 920 Cov.: 32 AF XY: 0.0624 AC XY: 4644 AN XY: 74390

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.0783

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00159

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0409 Hom.: 91

Bravo AF: 0.0718

Asia WGS AF: 0.0420 AC: 145 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.84

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: rs2300622; hg19: chr6-146725443;