chr7-126779358-C-A

Variant names:

• chr7-126779358-C-A
• rs12534101
• NM_000845.3:c.1157-9293G>T

Variant summary

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	NM_000845.3	MANE Select	c.1157-9293G>T		intron	N/A	NP_000836.2	O00222-1
	GRM8	NM_001371086.1		c.1157-9293G>T		intron	N/A	NP_001358015.1	A0A9L9PYG5
	GRM8	NM_001127323.1		c.1157-9293G>T		intron	N/A	NP_001120795.1	O00222-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	ENST00000339582.7	TSL:5 MANE Select	c.1157-9293G>T		intron	N/A	ENSP00000344173.2	O00222-1
	GRM8	ENST00000358373.8	TSL:1	c.1157-9293G>T		intron	N/A	ENSP00000351142.3	O00222-2
	GRM8	ENST00000341617.7	TSL:1	n.1157-9293G>T		intron	N/A	ENSP00000345747.3	O00222-3

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

African (AFR) AF: 0.200 AC: 8275 AN: 41418

American (AMR) AF: 0.347 AC: 5279 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1456 AN: 3470

East Asian (EAS) AF: 0.428 AC: 2207 AN: 5154

South Asian (SAS) AF: 0.410 AC: 1972 AN: 4806

European-Finnish (FIN) AF: 0.308 AC: 3234 AN: 10500

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23725 AN: 67840

Other (OTH) AF: 0.333 AC: 701 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.50
PhyloP100		0.072
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: rs12534101; hg19: chr7-126419412;