rs1361995

Variant names:

• chr7-126732003-C-T
• rs1361995
• NM_000845.3:c.1357+37862G>A

Variant summary

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

The NM_000845.3(GRM8):​c.1357+37862G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,550 control chromosomes in the GnomAD database, including 9,644 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 0.35 (9644 hom., cov: 31)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.1357+37862G>A		intron_variant	Intron 7 of 10	ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.1357+37862G>A		intron_variant	Intron 7 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52883 AN: 151432 Hom.: 9630 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.349 AC: 52932 AN: 151550 Hom.: 9644 Cov.: 31 AF XY: 0.352 AC XY: 26089 AN XY: 74050

African (AFR) AF: 0.307 AC: 12677 AN: 41326

American (AMR) AF: 0.340 AC: 5178 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1211 AN: 3466

East Asian (EAS) AF: 0.0706 AC: 364 AN: 5156

South Asian (SAS) AF: 0.338 AC: 1627 AN: 4814

European-Finnish (FIN) AF: 0.467 AC: 4887 AN: 10464

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 25990 AN: 67804

Other (OTH) AF: 0.327 AC: 688 AN: 2104

Alfa AF: 0.364 Hom.: 3895

Bravo AF: 0.334

Asia WGS AF: 0.236 AC: 813 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.27
PhyloP100		-0.13
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: rs1361995; hg19: chr7-126372057;