7-127078156-C-A

Position:

• chr7-127078156-C-A

Variant summary

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

The NM_000845.3(GRM8):​c.727+28340G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,204 control chromosomes in the GnomAD database, including 2,074 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 0.11 (2074 hom., cov: 33)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

GRM8 (HGNC:4600): (glutamate metabotropic receptor 8) 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 metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM8	NM_000845.3	c.727+28340G>T		intron_variant		ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.727+28340G>T		intron_variant		5	NM_000845.3	ENSP00000344173	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17308 AN: 152086 Hom.: 2067 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0459

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0401

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.114 AC: 17345 AN: 152204 Hom.: 2074 Cov.: 33 AF XY: 0.111 AC XY: 8280 AN XY: 74418

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.0674

Gnomad4 ASJ AF: 0.0459

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0382

Gnomad4 FIN AF: 0.0315

Gnomad4 NFE AF: 0.0401

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0711 Hom.: 200

Bravo AF: 0.127

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.090
DANN	Benign	0.70

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: rs2106190; hg19: chr7-126718210;