7-126716913-G-T

Variant names:

• chr7-126716913-G-T
• rs2299495
• NM_000845.3:c.1357+52952C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000845.3(GRM8):​c.1357+52952C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,984 control chromosomes in the GnomAD database, including 2,389 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 0.17 (2389 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.1357+52952C>A		intron_variant	Intron 7 of 10	ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.1357+52952C>A		intron_variant	Intron 7 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26190 AN: 151866 Hom.: 2386 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.172 AC: 26205 AN: 151984 Hom.: 2389 Cov.: 32 AF XY: 0.172 AC XY: 12742 AN XY: 74288

African (AFR) AF: 0.198 AC: 8194 AN: 41428

American (AMR) AF: 0.161 AC: 2458 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3468

East Asian (EAS) AF: 0.167 AC: 861 AN: 5144

South Asian (SAS) AF: 0.164 AC: 788 AN: 4816

European-Finnish (FIN) AF: 0.130 AC: 1377 AN: 10564

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11304 AN: 67986

Other (OTH) AF: 0.190 AC: 402 AN: 2112

Alfa AF: 0.113 Hom.: 214

Bravo AF: 0.173

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.33
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2299495; hg19: chr7-126356967;