rs7796270

Variant names:

• chr7-126997621-G-A
• rs7796270
• NM_000845.3:c.728-92938C>T

Variant summary

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

The NM_000845.3(GRM8):​c.728-92938C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 149,956 control chromosomes in the GnomAD database, including 8,065 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 0.32 (8065 hom., cov: 30)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.728-92938C>T		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.728-92938C>T		intron_variant	Intron 3 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48036 AN: 149852 Hom.: 8053 Cov.: 30

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0462

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.321 AC: 48081 AN: 149956 Hom.: 8065 Cov.: 30 AF XY: 0.319 AC XY: 23326 AN XY: 73072

African (AFR) AF: 0.395 AC: 16168 AN: 40978

American (AMR) AF: 0.307 AC: 4625 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3460

East Asian (EAS) AF: 0.0456 AC: 234 AN: 5136

South Asian (SAS) AF: 0.303 AC: 1448 AN: 4780

European-Finnish (FIN) AF: 0.286 AC: 2817 AN: 9862

Middle Eastern (MID) AF: 0.365 AC: 105 AN: 288

European-Non Finnish (NFE) AF: 0.310 AC: 20876 AN: 67370

Other (OTH) AF: 0.322 AC: 674 AN: 2094

Alfa AF: 0.314 Hom.: 951

Bravo AF: 0.325

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.69
PhyloP100		-0.61
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: rs7796270; hg19: chr7-126637675;