rs2237808

Positions:

• chr7-127227851-A-G
• chr7-127227851-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000845.3(GRM8):​c.510+14844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,070 control chromosomes in the GnomAD database, including 29,467 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 0.59 (29467 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636

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]

GRM8-AS1 (HGNC:40268): (GRM8 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM8	NM_000845.3	c.510+14844T>C		intron_variant		ENST00000339582.7	NP_000836.2
GRM8-AS1	NR_110194.1	n.364-522A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.510+14844T>C		intron_variant		5	NM_000845.3	ENSP00000344173	P1
GRM8-AS1	ENST00000667616.1	n.128-522A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89920 AN: 151952 Hom.: 29413 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.592 AC: 90025 AN: 152070 Hom.: 29467 Cov.: 32 AF XY: 0.583 AC XY: 43303 AN XY: 74326

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.578

Alfa AF: 0.556 Hom.: 3133

Bravo AF: 0.606

Asia WGS AF: 0.396 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.25
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs2237808; hg19: chr7-126867905;