chr6-146437188-T-C

Position:

• chr6-146437188-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001278064.2(GRM1):​c.*2392T>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 0.505 in 151,920 control chromosomes in the GnomAD database, including 19,425 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 0.50 (19425 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GRM1 NM_001278064.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.827

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM1	NM_001278064.2	c.*2392T>C		3_prime_UTR_variant	8/8	ENST00000282753.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM1	ENST00000282753.6	c.*2392T>C		3_prime_UTR_variant	8/8	1	NM_001278064.2	P1
GRM1	ENST00000492807.6	c.*3341T>C		3_prime_UTR_variant	10/10	1
GRM1	ENST00000361719.6	c.*2392T>C		3_prime_UTR_variant	9/9	5		P1
GRM1	ENST00000706836.1	c.*3341T>C		3_prime_UTR_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76581 AN: 151804 Hom.: 19398 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.505 AC: 76644 AN: 151920 Hom.: 19425 Cov.: 32 AF XY: 0.502 AC XY: 37274 AN XY: 74234

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.515

Alfa AF: 0.507 Hom.: 7706

Bravo AF: 0.501

Asia WGS AF: 0.573 AC: 1989 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.9
DANN	Benign	0.82

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: rs362821; hg19: chr6-146758324;