chr6-146436074-T-C

Position:

• chr6-146436074-T-C

Variant summary

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

The NM_001278064.2(GRM1):​c.*1278T>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 0.641 in 152,028 control chromosomes in the GnomAD database, including 33,122 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 (33078 hom., cov: 32)
  • Exomes 𝑓: 0.45 (44 hom.)
• Consequence: GRM1 NM_001278064.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM1	NM_001278064.2	c.*1278T>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.*1278T>C		3_prime_UTR_variant	8/8	1	NM_001278064.2	ENSP00000282753.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97149 AN: 151472 Hom.: 33020 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.447 AC: 196 AN: 438 Hom.: 44 Cov.: 0 AF XY: 0.436 AC XY: 115 AN XY: 264

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.642 AC: 97264 AN: 151590 Hom.: 33078 Cov.: 32 AF XY: 0.636 AC XY: 47118 AN XY: 74034

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.630

Alfa AF: 0.508 Hom.: 3096

Bravo AF: 0.654

Asia WGS AF: 0.640 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.80
DANN	Benign	0.28

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: rs3804294; hg19: chr6-146757210;