chr7-127024065-T-C

Variant names:

• chr7-127024065-T-C
• rs17863182
• NM_000845.3:c.727+82431A>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+82431A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 152,166 control chromosomes in the GnomAD database, including 524 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 0.070 (524 hom., cov: 33)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.727+82431A>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+82431A>G		intron_variant	Intron 3 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10608 AN: 152048 Hom.: 526 Cov.: 33

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0692

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00348

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0697 AC: 10602 AN: 152166 Hom.: 524 Cov.: 33 AF XY: 0.0690 AC XY: 5135 AN XY: 74390

African (AFR) AF: 0.0164 AC: 681 AN: 41552

American (AMR) AF: 0.0691 AC: 1056 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 477 AN: 3466

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5164

South Asian (SAS) AF: 0.120 AC: 579 AN: 4812

European-Finnish (FIN) AF: 0.0732 AC: 776 AN: 10600

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0997 AC: 6774 AN: 67970

Other (OTH) AF: 0.0780 AC: 165 AN: 2116

Alfa AF: 0.0784 Hom.: 73

Bravo AF: 0.0642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.60
PhyloP100		1.3
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: rs17863182; hg19: chr7-126664119;