chr7-127057596-T-C

Variant names:

• chr7-127057596-T-C
• rs6467108
• NM_000845.3:c.727+48900A>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.727+48900A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 152,216 control chromosomes in the GnomAD database, including 526 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 0.080 (526 hom., cov: 33)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.727+48900A>G		intron_variant	Intron 3 of 10	ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.727+48900A>G		intron_variant	Intron 3 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12114 AN: 152100 Hom.: 522 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0844

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0574

Gnomad OTH AF: 0.0836

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

GnomAD4 genome AF: 0.0797 AC: 12138 AN: 152216 Hom.: 526 Cov.: 33 AF XY: 0.0812 AC XY: 6042 AN XY: 74430

African (AFR) AF: 0.111 AC: 4600 AN: 41526

American (AMR) AF: 0.0848 AC: 1298 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3468

East Asian (EAS) AF: 0.109 AC: 565 AN: 5178

South Asian (SAS) AF: 0.126 AC: 608 AN: 4826

European-Finnish (FIN) AF: 0.0548 AC: 580 AN: 10592

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0574 AC: 3905 AN: 68004

Other (OTH) AF: 0.0836 AC: 177 AN: 2116

Alfa AF: 0.0738 Hom.: 76

Bravo AF: 0.0839

Asia WGS AF: 0.107 AC: 371 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.63
PhyloP100		-0.44
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: rs6467108; hg19: chr7-126697650;