chr7-126522866-T-C

Variant names:

• chr7-126522866-T-C
• rs1362178
• NM_000845.3:c.2430+10086A>G

Variant summary

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

The NM_000845.3(GRM8):​c.2430+10086A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,128 control chromosomes in the GnomAD database, including 49,263 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 0.80 (49263 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755
• Publications: 3 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]

ENSG00000287568 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	NM_000845.3	MANE Select	c.2430+10086A>G		intron	N/A	NP_000836.2
	GRM8	NM_001371086.1		c.2430+10086A>G		intron	N/A	NP_001358015.1
	GRM8	NM_001127323.1		c.2430+10086A>G		intron	N/A	NP_001120795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	ENST00000339582.7	TSL:5 MANE Select	c.2430+10086A>G		intron	N/A	ENSP00000344173.2
	GRM8	ENST00000358373.8	TSL:1	c.2430+10086A>G		intron	N/A	ENSP00000351142.3
	GRM8	ENST00000341617.7	TSL:1	n.*995+10086A>G		intron	N/A	ENSP00000345747.3

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122128 AN: 152010 Hom.: 49214 Cov.: 32

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.793

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

GnomAD4 genome AF: 0.804 AC: 122240 AN: 152128 Hom.: 49263 Cov.: 32 AF XY: 0.799 AC XY: 59430 AN XY: 74364

African (AFR) AF: 0.867 AC: 35972 AN: 41488

American (AMR) AF: 0.757 AC: 11560 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 2805 AN: 3468

East Asian (EAS) AF: 0.816 AC: 4227 AN: 5180

South Asian (SAS) AF: 0.809 AC: 3901 AN: 4824

European-Finnish (FIN) AF: 0.751 AC: 7948 AN: 10584

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53191 AN: 67994

Other (OTH) AF: 0.794 AC: 1673 AN: 2108

Alfa AF: 0.793 Hom.: 196687

Bravo AF: 0.809

Asia WGS AF: 0.819 AC: 2849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.54
PhyloP100		-0.76
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: rs1362178; hg19: chr7-126162920;