rs7778604

Variant names:

• chr7-127006426-C-T
• rs7778604
• NM_000845.3:c.727+100070G>A

Variant summary

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

The ENST00000339582.7(GRM8):​c.727+100070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 151,926 control chromosomes in the GnomAD database, including 1,245 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 0.12 (1245 hom., cov: 32)
• Consequence: GRM8 ENST00000339582.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 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.727+100070G>A		intron	N/A	NP_000836.2
	GRM8	NM_001371086.1		c.727+100070G>A		intron	N/A	NP_001358015.1
	GRM8	NM_001127323.1		c.727+100070G>A		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.727+100070G>A		intron	N/A	ENSP00000344173.2
	GRM8	ENST00000358373.8	TSL:1	c.727+100070G>A		intron	N/A	ENSP00000351142.3
	GRM8	ENST00000341617.7	TSL:1	n.727+100070G>A		intron	N/A	ENSP00000345747.3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17759 AN: 151808 Hom.: 1247 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00329

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0993

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.117 AC: 17769 AN: 151926 Hom.: 1245 Cov.: 32 AF XY: 0.114 AC XY: 8479 AN XY: 74258

African (AFR) AF: 0.180 AC: 7480 AN: 41442

American (AMR) AF: 0.0905 AC: 1378 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 487 AN: 3466

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5156

South Asian (SAS) AF: 0.119 AC: 574 AN: 4820

European-Finnish (FIN) AF: 0.0734 AC: 778 AN: 10600

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0993 AC: 6741 AN: 67892

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.103 Hom.: 457

Bravo AF: 0.119

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.80
PhyloP100		-1.2
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: rs7778604; hg19: chr7-126646480;