7-127223262-C-T

Variant names:

• chr7-127223262-C-T
• rs6960871
• NM_000845.3:c.510+19433G>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.510+19433G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,800 control chromosomes in the GnomAD database, including 25,200 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 0.55 (25200 hom., cov: 31)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• 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]

GRM8-AS1 (HGNC:40268): (GRM8 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.510+19433G>A		intron_variant	Intron 2 of 10	ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.510+19433G>A		intron_variant	Intron 2 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83157 AN: 151680 Hom.: 25151 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.548 AC: 83256 AN: 151800 Hom.: 25200 Cov.: 31 AF XY: 0.539 AC XY: 39976 AN XY: 74142

African (AFR) AF: 0.803 AC: 33257 AN: 41398

American (AMR) AF: 0.405 AC: 6183 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1715 AN: 3468

East Asian (EAS) AF: 0.119 AC: 614 AN: 5156

South Asian (SAS) AF: 0.442 AC: 2118 AN: 4792

European-Finnish (FIN) AF: 0.450 AC: 4720 AN: 10484

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32764 AN: 67948

Other (OTH) AF: 0.538 AC: 1130 AN: 2102

Alfa AF: 0.545 Hom.: 13218

Bravo AF: 0.554

Asia WGS AF: 0.333 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.8
DANN	Benign	0.43
PhyloP100		0.72
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: rs6960871; hg19: chr7-126863316;