chr7-127149882-G-C

Variant names:

• chr7-127149882-G-C
• rs17865314
• NM_000845.3:c.511-43170C>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.511-43170C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,944 control chromosomes in the GnomAD database, including 3,008 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 0.11 (3008 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944
• Publications: 1 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=-1.12).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.511-43170C>G		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.511-43170C>G		intron_variant	Intron 2 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16768 AN: 151826 Hom.: 3003 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00394

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.111 AC: 16791 AN: 151944 Hom.: 3008 Cov.: 32 AF XY: 0.106 AC XY: 7876 AN XY: 74294

African (AFR) AF: 0.374 AC: 15495 AN: 41380

American (AMR) AF: 0.0487 AC: 743 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00750 AC: 26 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5154

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00394 AC: 268 AN: 67940

Other (OTH) AF: 0.102 AC: 216 AN: 2110

Alfa AF: 0.0880 Hom.: 214

Bravo AF: 0.128

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.29
DANN	Benign	0.33
PhyloP100		-0.94
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: rs17865314; hg19: chr7-126789936;