chr6-146029128-T-C

Position:

• chr6-146029128-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001278064.2(GRM1):​c.-390T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 319,312 control chromosomes in the GnomAD database, including 31,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (15158 hom., cov: 33)
  • Exomes 𝑓: 0.44 (16461 hom.)
• Consequence: GRM1 NM_001278064.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.398

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-146029128-T-C is Benign according to our data. Variant chr6-146029128-T-C is described in ClinVar as [Benign]. Clinvar id is 1253600.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM1	NM_001278064.2	c.-390T>C		5_prime_UTR_variant	1/8	ENST00000282753.6	NP_001264993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM1	ENST00000282753.6	c.-390T>C		5_prime_UTR_variant	1/8	1	NM_001278064.2	ENSP00000282753	P1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67279 AN: 152020 Hom.: 15141 Cov.: 33

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.436 AC: 72914 AN: 167174 Hom.: 16461 AF XY: 0.441 AC XY: 39367 AN XY: 89278

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.415

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.437

GnomAD4 genome AF: 0.443 AC: 67331 AN: 152138 Hom.: 15158 Cov.: 33 AF XY: 0.444 AC XY: 33060 AN XY: 74388

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.452

Alfa AF: 0.434 Hom.: 2342

Bravo AF: 0.434

Asia WGS AF: 0.464 AC: 1615 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 25, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2073287; hg19: chr6-146350264;