7-126551122-T-C

Variant names:

• chr7-126551122-T-C
• rs2402816
• NM_000845.3:c.1495-17235A>G

Variant summary

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

The NM_000845.3(GRM8):​c.1495-17235A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,996 control chromosomes in the GnomAD database, including 8,953 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 0.34 (8953 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 2 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 (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.1495-17235A>G		intron_variant	Intron 8 of 10	ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.1495-17235A>G		intron_variant	Intron 8 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50978 AN: 151878 Hom.: 8955 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.335 AC: 50988 AN: 151996 Hom.: 8953 Cov.: 32 AF XY: 0.336 AC XY: 24944 AN XY: 74308

African (AFR) AF: 0.240 AC: 9955 AN: 41500

American (AMR) AF: 0.295 AC: 4508 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1216 AN: 3464

East Asian (EAS) AF: 0.457 AC: 2364 AN: 5172

South Asian (SAS) AF: 0.464 AC: 2232 AN: 4814

European-Finnish (FIN) AF: 0.334 AC: 3513 AN: 10524

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.384 AC: 26111 AN: 67946

Other (OTH) AF: 0.340 AC: 718 AN: 2110

Alfa AF: 0.377 Hom.: 6680

Bravo AF: 0.324

Asia WGS AF: 0.463 AC: 1610 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.017
DANN	Benign	0.60
PhyloP100		-2.2
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: rs2402816; hg19: chr7-126191176;