chr6-146028514-C-T

Position:

• chr6-146028514-C-T

Variant summary

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

The NM_001278065.2(GRM1):​c.-320-684C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,266 control chromosomes in the GnomAD database, including 12,549 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 0.40 (12549 hom., cov: 29)
• Consequence: GRM1 NM_001278065.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

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]

GRM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• 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_001278065.2	c.-320-684C>T		intron_variant			NP_001264994.1
GRM1	XM_011535782.2	c.-323-681C>T		intron_variant			XP_011534084.1
GRM1	XM_017010783.2	c.-320-684C>T		intron_variant			XP_016866272.1
GRM1	XM_017010784.2	c.-320-684C>T		intron_variant			XP_016866273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM1	ENST00000492807.6	c.-320-684C>T		intron_variant		1		ENSP00000424095.1
GRM1	ENST00000361719.6	c.-320-684C>T		intron_variant		5		ENSP00000354896.2
GRM1	ENST00000706833.1	c.-323-681C>T		intron_variant				ENSP00000516579.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 60942 AN: 151146 Hom.: 12533 Cov.: 29

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.403 AC: 60987 AN: 151266 Hom.: 12549 Cov.: 29 AF XY: 0.406 AC XY: 29958 AN XY: 73838

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.416

Alfa AF: 0.257 Hom.: 585

Bravo AF: 0.387

Asia WGS AF: 0.458 AC: 1593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.4
DANN	Benign	0.70

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: rs854145; hg19: chr6-146349650;