chr7-127204480-T-G

Variant names:

• chr7-127204480-T-G
• rs3808117
• NM_000845.3:c.510+38215A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000845.3(GRM8):​c.510+38215A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,134 control chromosomes in the GnomAD database, including 2,497 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 0.17 (2497 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.510+38215A>C		intron_variant	Intron 2 of 10	ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.510+38215A>C		intron_variant	Intron 2 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26414 AN: 152016 Hom.: 2495 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.174 AC: 26424 AN: 152134 Hom.: 2497 Cov.: 32 AF XY: 0.175 AC XY: 13041 AN XY: 74366

African (AFR) AF: 0.126 AC: 5238 AN: 41528

American (AMR) AF: 0.145 AC: 2210 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1142 AN: 3470

East Asian (EAS) AF: 0.100 AC: 519 AN: 5170

South Asian (SAS) AF: 0.165 AC: 795 AN: 4820

European-Finnish (FIN) AF: 0.202 AC: 2144 AN: 10588

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.202 AC: 13723 AN: 67962

Other (OTH) AF: 0.193 AC: 408 AN: 2110

Alfa AF: 0.187 Hom.: 1689

Bravo AF: 0.167

Asia WGS AF: 0.143 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Benign	0.72
PhyloP100		1.7
Mutation Taster		=99/1	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: rs3808117; hg19: chr7-126844534;