rs41285865

chr6-146436940-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001278064.2(GRM1):c.*2144C>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 0.0105 in 152,180 control chromosomes in the GnomAD database, including 13 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 0.010 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GRM1 NM_001278064.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.78).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0105 (1596/152180) while in subpopulation AMR AF= 0.0167 (256/15290). AF 95% confidence interval is 0.0151. There are 13 homozygotes in gnomad4. There are 745 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM1	NM_001278064.2	c.*2144C>T		3_prime_UTR_variant	8/8	ENST00000282753.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM1	ENST00000282753.6	c.*2144C>T		3_prime_UTR_variant	8/8	1	NM_001278064.2	P1
GRM1	ENST00000492807.6	c.*3093C>T		3_prime_UTR_variant	10/10	1
GRM1	ENST00000361719.6	c.*2144C>T		3_prime_UTR_variant	9/9	5		P1
GRM1	ENST00000706836.1	c.*3093C>T		3_prime_UTR_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1596 AN: 152062 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00295

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0177

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 432 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 260

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0105 AC: 1596 AN: 152180 Hom.: 13 Cov.: 33 AF XY: 0.0100 AC XY: 745 AN XY: 74392

Gnomad4 AFR AF: 0.00294

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00561

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0147 Hom.: 2

Bravo AF: 0.0116

Asia WGS AF: 0.00231 AC: 8 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.4
Dann	Benign	0.63

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: rs41285865; hg19: chr6-146758076;