rs11971186

Variant names:

• chr7-126797843-A-G
• rs11971186
• NM_000845.3:c.1157-27778T>C

Variant summary

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

The NM_000845.3(GRM8):​c.1157-27778T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,988 control chromosomes in the GnomAD database, including 7,924 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 0.31 (7924 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.1157-27778T>C		intron_variant	Intron 6 of 10	ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.1157-27778T>C		intron_variant	Intron 6 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47630 AN: 151872 Hom.: 7930 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.313 AC: 47633 AN: 151988 Hom.: 7924 Cov.: 32 AF XY: 0.313 AC XY: 23249 AN XY: 74312

African (AFR) AF: 0.209 AC: 8681 AN: 41486

American (AMR) AF: 0.346 AC: 5276 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3462

East Asian (EAS) AF: 0.413 AC: 2136 AN: 5166

South Asian (SAS) AF: 0.414 AC: 2001 AN: 4828

European-Finnish (FIN) AF: 0.308 AC: 3257 AN: 10564

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23719 AN: 67928

Other (OTH) AF: 0.332 AC: 698 AN: 2102

Alfa AF: 0.346 Hom.: 22448

Bravo AF: 0.313

Asia WGS AF: 0.399 AC: 1388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.49
PhyloP100		1.0
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: rs11971186; hg19: chr7-126437897;