5-178984314-C-T

Position:

• chr5-178984314-C-T

Variant summary

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

The NM_000843.4(GRM6):​c.2125-1093G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 151,904 control chromosomes in the GnomAD database, including 66,353 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 0.93 (66353 hom., cov: 33)
• Consequence: GRM6 NM_000843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845

Genes affected

GRM6 (HGNC:4598): (glutamate metabotropic receptor 6) 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. Mutations in this gene result in congenital stationary night blindness type 1B. [provided by RefSeq, May 2018]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM6	NM_000843.4	c.2125-1093G>A		intron_variant		ENST00000517717.3	NP_000834.2
ZNF454	XR_007058600.1	n.5644-5433C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM6	ENST00000517717.3	c.2125-1093G>A		intron_variant		5	NM_000843.4	ENSP00000430767	P1
	ENST00000519491.1	n.305-5433C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.934 AC: 141734 AN: 151784 Hom.: 66307 Cov.: 33

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.934 AC: 141838 AN: 151904 Hom.: 66353 Cov.: 33 AF XY: 0.932 AC XY: 69195 AN XY: 74232

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.931

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.959

Gnomad4 NFE AF: 0.965

Gnomad4 OTH AF: 0.936

Alfa AF: 0.943 Hom.: 10181

Bravo AF: 0.932

Asia WGS AF: 0.895 AC: 3116 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	12
DANN	Benign	0.78

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: rs2645341; hg19: chr5-178411315;