NM_000845.3:c.510+38010T>C

Variant names:

• chr7-127204685-A-G
• rs1361957
• NM_000845.3:c.510+38010T>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.510+38010T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,948 control chromosomes in the GnomAD database, including 31,537 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 0.63 (31537 hom., cov: 31)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 0 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 (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	NM_000845.3	MANE Select	c.510+38010T>C		intron	N/A	NP_000836.2
	GRM8	NM_001371086.1		c.510+38010T>C		intron	N/A	NP_001358015.1
	GRM8	NM_001127323.1		c.510+38010T>C		intron	N/A	NP_001120795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	ENST00000339582.7	TSL:5 MANE Select	c.510+38010T>C		intron	N/A	ENSP00000344173.2
	GRM8	ENST00000358373.8	TSL:1	c.510+38010T>C		intron	N/A	ENSP00000351142.3
	GRM8	ENST00000341617.7	TSL:1	n.510+38010T>C		intron	N/A	ENSP00000345747.3

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95844 AN: 151830 Hom.: 31476 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.631 AC: 95955 AN: 151948 Hom.: 31537 Cov.: 31 AF XY: 0.626 AC XY: 46472 AN XY: 74248

African (AFR) AF: 0.786 AC: 32553 AN: 41442

American (AMR) AF: 0.482 AC: 7346 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2389 AN: 3468

East Asian (EAS) AF: 0.255 AC: 1314 AN: 5160

South Asian (SAS) AF: 0.516 AC: 2490 AN: 4826

European-Finnish (FIN) AF: 0.608 AC: 6393 AN: 10522

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41307 AN: 67958

Other (OTH) AF: 0.640 AC: 1351 AN: 2110

Alfa AF: 0.617 Hom.: 5938

Bravo AF: 0.626

Asia WGS AF: 0.435 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.67
PhyloP100		-0.30
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: rs1361957; hg19: chr7-126844739;