rs12534101

chr7-126779358-C-Achr7-126779358-C-T

Variant summary

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

The NM_000845.3(GRM8):c.1157-9293G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,728 control chromosomes in the GnomAD database, including 7,856 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 0.31 (7856 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM8	NM_000845.3	c.1157-9293G>T		intron_variant		ENST00000339582.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM8	ENST00000339582.7	c.1157-9293G>T		intron_variant		5	NM_000845.3	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47255 AN: 151610 Hom.: 7859 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.311 AC: 47262 AN: 151728 Hom.: 7856 Cov.: 32 AF XY: 0.311 AC XY: 23030 AN XY: 74124

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.333

Alfa AF: 0.322 Hom.: 1038

Bravo AF: 0.311

Asia WGS AF: 0.405 AC: 1390 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.1
Dann	Benign	0.50

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: rs12534101; hg19: chr7-126419412;