6-146181904-A-G

Position:

• chr6-146181904-A-G

Variant summary

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

The NM_001278064.2(GRM1):​c.950+22307A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,122 control chromosomes in the GnomAD database, including 918 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 0.10 (918 hom., cov: 32)
• Consequence: GRM1 NM_001278064.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591

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 (SAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM1	NM_001278064.2	c.950+22307A>G		intron_variant		ENST00000282753.6	NP_001264993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM1	ENST00000282753.6	c.950+22307A>G		intron_variant		1	NM_001278064.2	ENSP00000282753.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15761 AN: 152004 Hom.: 918 Cov.: 32

Gnomad AFR AF: 0.0591

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.0951

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0733

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0955

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.104 AC: 15764 AN: 152122 Hom.: 918 Cov.: 32 AF XY: 0.104 AC XY: 7759 AN XY: 74360

Gnomad4 AFR AF: 0.0590

Gnomad4 AMR AF: 0.0949

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0733

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.0955

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.120

Alfa AF: 0.121 Hom.: 1553

Bravo AF: 0.100

Asia WGS AF: 0.111 AC: 384 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.61

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: rs13218303; hg19: chr6-146503040;