rs2402820

Variant names:

• chr7-126657644-G-A
• rs2402820
• NM_000845.3:c.1358-48146C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-126657644-G-A
• chr7-126657644-G-C

Variant summary

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

The ENST00000339582.7(GRM8):​c.1358-48146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,152 control chromosomes in the GnomAD database, including 8,001 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 (8001 hom., cov: 33)
• Consequence: GRM8 ENST00000339582.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000339582.7. 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.1358-48146C>T		intron	N/A	NP_000836.2
	GRM8	NM_001371086.1		c.1358-48146C>T		intron	N/A	NP_001358015.1
	GRM8	NM_001127323.1		c.1358-48146C>T		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.1358-48146C>T		intron	N/A	ENSP00000344173.2
	GRM8	ENST00000358373.8	TSL:1	c.1358-48146C>T		intron	N/A	ENSP00000351142.3
	GRM8	ENST00000341617.7	TSL:1	n.1428+44113C>T		intron	N/A	ENSP00000345747.3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47561 AN: 152034 Hom.: 7979 Cov.: 33

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.313 AC: 47625 AN: 152152 Hom.: 8001 Cov.: 33 AF XY: 0.312 AC XY: 23179 AN XY: 74378

African (AFR) AF: 0.385 AC: 15971 AN: 41492

American (AMR) AF: 0.409 AC: 6251 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3472

East Asian (EAS) AF: 0.360 AC: 1865 AN: 5174

South Asian (SAS) AF: 0.278 AC: 1341 AN: 4824

European-Finnish (FIN) AF: 0.230 AC: 2429 AN: 10582

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17821 AN: 68008

Other (OTH) AF: 0.296 AC: 627 AN: 2116

Alfa AF: 0.287 Hom.: 3685

Bravo AF: 0.334

Asia WGS AF: 0.313 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.51
PhyloP100		-0.22
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: rs2402820; hg19: chr7-126297698;