rs2237801

Variant names:

• chr7-127205704-C-T
• rs2237801
• NM_000845.3:c.510+36991G>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+36991G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,916 control chromosomes in the GnomAD database, including 14,729 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 0.41 (14729 hom., cov: 31)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 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+36991G>A		intron	N/A	NP_000836.2
	GRM8	NM_001371086.1		c.510+36991G>A		intron	N/A	NP_001358015.1
	GRM8	NM_001127323.1		c.510+36991G>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+36991G>A		intron	N/A	ENSP00000344173.2
	GRM8	ENST00000358373.8	TSL:1	c.510+36991G>A		intron	N/A	ENSP00000351142.3
	GRM8	ENST00000341617.7	TSL:1	n.510+36991G>A		intron	N/A	ENSP00000345747.3

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62292 AN: 151798 Hom.: 14684 Cov.: 31

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.411 AC: 62396 AN: 151916 Hom.: 14729 Cov.: 31 AF XY: 0.408 AC XY: 30319 AN XY: 74262

African (AFR) AF: 0.654 AC: 27079 AN: 41410

American (AMR) AF: 0.301 AC: 4599 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1637 AN: 3462

East Asian (EAS) AF: 0.151 AC: 777 AN: 5158

South Asian (SAS) AF: 0.290 AC: 1394 AN: 4804

European-Finnish (FIN) AF: 0.331 AC: 3499 AN: 10578

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22136 AN: 67926

Other (OTH) AF: 0.411 AC: 869 AN: 2112

Alfa AF: 0.346 Hom.: 5789

Bravo AF: 0.417

Asia WGS AF: 0.265 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.37
PhyloP100		0.12
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: rs2237801; hg19: chr7-126845758;