rs17161018

Variant names:

• chr7-86815615-G-A
• rs17161018
• NM_000840.3:c.1325-23224G>A

Variant summary

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

The NM_000840.3(GRM3):​c.1325-23224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 151,774 control chromosomes in the GnomAD database, including 634 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 0.077 (634 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 1 publications found

Genes affected

GRM3 (HGNC:4595): (glutamate metabotropic receptor 3) 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. [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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM3	NM_000840.3	c.1325-23224G>A		intron_variant	Intron 3 of 5	ENST00000361669.7	NP_000831.2
GRM3	NM_001363522.2	c.1324+28499G>A		intron_variant	Intron 3 of 4		NP_001350451.1
GRM3	XM_047420268.1	c.1325-23224G>A		intron_variant	Intron 4 of 6		XP_047276224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM3	ENST00000361669.7	c.1325-23224G>A		intron_variant	Intron 3 of 5	1	NM_000840.3	ENSP00000355316.2
GRM3	ENST00000439827.1	c.1324+28499G>A		intron_variant	Intron 3 of 4	1		ENSP00000398767.1

Frequencies

GnomAD3 genomes AF: 0.0769 AC: 11658 AN: 151656 Hom.: 634 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0768 AC: 11658 AN: 151774 Hom.: 634 Cov.: 32 AF XY: 0.0735 AC XY: 5449 AN XY: 74184

African (AFR) AF: 0.0217 AC: 900 AN: 41452

American (AMR) AF: 0.0806 AC: 1225 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 307 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0216 AC: 104 AN: 4816

European-Finnish (FIN) AF: 0.0609 AC: 643 AN: 10562

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8122 AN: 67796

Other (OTH) AF: 0.0991 AC: 209 AN: 2110

Alfa AF: 0.102 Hom.: 454

Bravo AF: 0.0757

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		1.2
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: rs17161018; hg19: chr7-86444931;