rs362822

Positions:

• chr6-146437406-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.*2610C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,222 control chromosomes in the GnomAD database, including 19,787 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 (19746 hom., cov: 31)
  • Exomes 𝑓: 0.43 (41 hom.)
• Consequence: GRM1 NM_001278064.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37

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=-0.48).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM1	NM_001278064.2	c.*2610C>T		3_prime_UTR_variant	8/8	ENST00000282753.6	NP_001264993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM1	ENST00000282753.6	c.*2610C>T		3_prime_UTR_variant	8/8	1	NM_001278064.2	ENSP00000282753	P1
GRM1	ENST00000492807.6	c.*3559C>T		3_prime_UTR_variant	10/10	1		ENSP00000424095
GRM1	ENST00000361719.6	c.*2610C>T		3_prime_UTR_variant	9/9	5		ENSP00000354896	P1
GRM1	ENST00000706836.1	c.*3559C>T		3_prime_UTR_variant	10/10			ENSP00000516582

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77248 AN: 151678 Hom.: 19719 Cov.: 31

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.428 AC: 184 AN: 430 Hom.: 41 Cov.: 0 AF XY: 0.411 AC XY: 106 AN XY: 258

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.509 AC: 77311 AN: 151792 Hom.: 19746 Cov.: 31 AF XY: 0.507 AC XY: 37582 AN XY: 74168

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.522

Alfa AF: 0.524 Hom.: 20343

Bravo AF: 0.505

Asia WGS AF: 0.574 AC: 1998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Benign	0.57

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: rs362822; hg19: chr6-146758542; COSMIC: COSV51387928; COSMIC: COSV51387928;