chr7-126738201-A-G

Variant names:

• chr7-126738201-A-G
• rs10487459
• NM_000845.3:c.1357+31664T>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.1357+31664T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,916 control chromosomes in the GnomAD database, including 8,646 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 (8646 hom., cov: 31)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.1357+31664T>C		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+31664T>C		intron_variant	Intron 7 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49318 AN: 151796 Hom.: 8635 Cov.: 31

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.0703

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.325 AC: 49367 AN: 151916 Hom.: 8646 Cov.: 31 AF XY: 0.329 AC XY: 24399 AN XY: 74212

African (AFR) AF: 0.224 AC: 9290 AN: 41478

American (AMR) AF: 0.333 AC: 5066 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3468

East Asian (EAS) AF: 0.0699 AC: 360 AN: 5150

South Asian (SAS) AF: 0.337 AC: 1623 AN: 4822

European-Finnish (FIN) AF: 0.465 AC: 4904 AN: 10538

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.382 AC: 25945 AN: 67924

Other (OTH) AF: 0.315 AC: 660 AN: 2098

Alfa AF: 0.341 Hom.: 1452

Bravo AF: 0.308

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.74
PhyloP100		0.40
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: rs10487459; hg19: chr7-126378255;