chr6-146424952-C-T

Position:

• chr6-146424952-C-T

Variant summary

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

The NM_001278064.2(GRM1):​c.2661-8920C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,998 control chromosomes in the GnomAD database, including 19,928 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 0.51 (19928 hom., cov: 33)
• Consequence: GRM1 NM_001278064.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM1	NM_001278064.2	c.2661-8920C>T		intron_variant		ENST00000282753.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM1	ENST00000282753.6	c.2661-8920C>T		intron_variant		1	NM_001278064.2	P1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77579 AN: 151880 Hom.: 19901 Cov.: 33

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.511 AC: 77646 AN: 151998 Hom.: 19928 Cov.: 33 AF XY: 0.509 AC XY: 37799 AN XY: 74296

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.521

Alfa AF: 0.519 Hom.: 10356

Bravo AF: 0.507

Asia WGS AF: 0.598 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.60

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: rs2268666; hg19: chr6-146746088; COSMIC: COSV51284317;