rs2106149

Variant names:

• chr7-127227234-C-T
• rs2106149
• NM_000845.3:c.510+15461G>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+15461G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,048 control chromosomes in the GnomAD database, including 29,362 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 0.59 (29362 hom., cov: 31)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 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.510+15461G>A		intron	N/A	NP_000836.2
	GRM8	NM_001371086.1		c.510+15461G>A		intron	N/A	NP_001358015.1
	GRM8	NM_001127323.1		c.510+15461G>A		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.510+15461G>A		intron	N/A	ENSP00000344173.2
	GRM8	ENST00000358373.8	TSL:1	c.510+15461G>A		intron	N/A	ENSP00000351142.3
	GRM8	ENST00000341617.7	TSL:1	n.510+15461G>A		intron	N/A	ENSP00000345747.3

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89709 AN: 151930 Hom.: 29308 Cov.: 31

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.591 AC: 89814 AN: 152048 Hom.: 29362 Cov.: 31 AF XY: 0.581 AC XY: 43208 AN XY: 74310

African (AFR) AF: 0.889 AC: 36898 AN: 41514

American (AMR) AF: 0.463 AC: 7061 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3472

East Asian (EAS) AF: 0.254 AC: 1313 AN: 5160

South Asian (SAS) AF: 0.452 AC: 2178 AN: 4818

European-Finnish (FIN) AF: 0.465 AC: 4918 AN: 10572

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33605 AN: 67938

Other (OTH) AF: 0.578 AC: 1218 AN: 2108

Alfa AF: 0.526 Hom.: 67901

Bravo AF: 0.604

Asia WGS AF: 0.396 AC: 1379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.51
DANN	Benign	0.66
PhyloP100		-1.4
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: rs2106149; hg19: chr7-126867288;