7-126532764-G-GATATATATAT

Position:

• chr7-126532764-G-GATATATATAT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000845.3(GRM8):​c.2430+187_2430+188insATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0019 (5 hom., cov: 0)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

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]

LOC101928357 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM8	NM_000845.3	c.2430+187_2430+188insATATATATAT		intron_variant		ENST00000339582.7
LOC101928357	XR_927937.3	n.215-1945_215-1936dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM8	ENST00000339582.7	c.2430+187_2430+188insATATATATAT		intron_variant		5	NM_000845.3	P1

Frequencies

GnomAD3 genomes AF: 0.00190 AC: 211 AN: 110892 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.000994

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00213

Gnomad EAS AF: 0.00106

Gnomad SAS AF: 0.00157

Gnomad FIN AF: 0.000433

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00271

Gnomad OTH AF: 0.00326

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

GnomAD4 genome AF: 0.00190 AC: 211 AN: 110916 Hom.: 5 Cov.: 0 AF XY: 0.00188 AC XY: 98 AN XY: 52266

Gnomad4 AFR AF: 0.000992

Gnomad4 AMR AF: 0.00125

Gnomad4 ASJ AF: 0.00213

Gnomad4 EAS AF: 0.00106

Gnomad4 SAS AF: 0.00158

Gnomad4 FIN AF: 0.000433

Gnomad4 NFE AF: 0.00271

Gnomad4 OTH AF: 0.00324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs521; hg19: chr7-126172818;