6-146435433-T-C

Position:

• chr6-146435433-T-C

Variant summary

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

The ENST00000282753.6(GRM1):​c.*637T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 156,822 control chromosomes in the GnomAD database, including 33,695 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 0.64 (32954 hom., cov: 33)
  • Exomes 𝑓: 0.53 (741 hom.)
• Consequence: GRM1 ENST00000282753.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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 (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM1	NM_001278064.2	c.*637T>C		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.*637T>C		3_prime_UTR_variant	8/8	1	NM_001278064.2	ENSP00000282753	P1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97216 AN: 151978 Hom.: 32898 Cov.: 33

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.526 AC: 2485 AN: 4726 Hom.: 741 Cov.: 0 AF XY: 0.520 AC XY: 1265 AN XY: 2432

Gnomad4 AFR exome AF: 0.955

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.573

Gnomad4 SAS exome AF: 0.590

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.550

Gnomad4 OTH exome AF: 0.609

GnomAD4 genome AF: 0.640 AC: 97328 AN: 152096 Hom.: 32954 Cov.: 33 AF XY: 0.635 AC XY: 47204 AN XY: 74356

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.630

Alfa AF: 0.535 Hom.: 3962

Bravo AF: 0.651

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.054
DANN	Benign	0.44

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: rs362819; hg19: chr6-146756569;