rs2071247

Variant names:

• chr5-178983150-C-T
• rs2071247
• NM_000843.4:c.2196G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-178983150-C-T
• chr5-178983150-C-A
• chr5-178983150-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000843.4(GRM6):​c.2196G>A​(p.Thr732Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,613,502 control chromosomes in the GnomAD database, including 26,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2846 hom., cov: 33)
  • Exomes 𝑓: 0.17 (23527 hom.)
• Consequence: GRM6 NM_000843.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -5.84
• Publications: 14 publications found

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]

ENSG00000254035 (HGNC:):

ZNF454 (HGNC:21200): (zinc finger protein 454) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 5-178983150-C-T is Benign according to our data. Variant chr5-178983150-C-T is described in ClinVar as Benign. ClinVar VariationId is 99643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM6	NM_000843.4	MANE Select	c.2196G>A	p.Thr732Thr	synonymous	Exon 10 of 11	NP_000834.2	O15303

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM6	ENST00000517717.3	TSL:5 MANE Select	c.2196G>A	p.Thr732Thr	synonymous	Exon 10 of 11	ENSP00000430767.1	O15303
	GRM6	ENST00000231188.9	TSL:2	c.2196G>A	p.Thr732Thr	synonymous	Exon 9 of 10	ENSP00000231188.5	O15303
	GRM6	ENST00000650031.1		c.2196G>A	p.Thr732Thr	synonymous	Exon 11 of 12	ENSP00000497110.1	O15303

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28558 AN: 152022 Hom.: 2841 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.203

GnomAD2 exomes AF: 0.202 AC: 50710 AN: 251112 AF XY: 0.205

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.375

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.172 AC: 251063 AN: 1461362 Hom.: 23527 Cov.: 34 AF XY: 0.175 AC XY: 127512 AN XY: 726992

African (AFR) AF: 0.206 AC: 6887 AN: 33470

American (AMR) AF: 0.189 AC: 8452 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 4167 AN: 26136

East Asian (EAS) AF: 0.396 AC: 15704 AN: 39698

South Asian (SAS) AF: 0.279 AC: 24054 AN: 86248

European-Finnish (FIN) AF: 0.175 AC: 9316 AN: 53204

Middle Eastern (MID) AF: 0.194 AC: 1119 AN: 5768

European-Non Finnish (NFE) AF: 0.153 AC: 170480 AN: 1111738

Other (OTH) AF: 0.180 AC: 10884 AN: 60380

GnomAD4 genome AF: 0.188 AC: 28598 AN: 152140 Hom.: 2846 Cov.: 33 AF XY: 0.192 AC XY: 14252 AN XY: 74378

African (AFR) AF: 0.205 AC: 8524 AN: 41504

American (AMR) AF: 0.187 AC: 2860 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 581 AN: 3472

East Asian (EAS) AF: 0.380 AC: 1956 AN: 5154

South Asian (SAS) AF: 0.295 AC: 1421 AN: 4818

European-Finnish (FIN) AF: 0.178 AC: 1892 AN: 10606

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10773 AN: 67980

Other (OTH) AF: 0.208 AC: 440 AN: 2112

Alfa AF: 0.168 Hom.: 3445

Bravo AF: 0.188

Asia WGS AF: 0.334 AC: 1158 AN: 3478

EpiCase AF: 0.167

EpiControl AF: 0.168

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (3)
-	-	1	Congenital stationary night blindness 1B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.043
DANN	Benign	0.88
PhyloP100		-5.8
Mutation Taster		=96/4	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: rs2071247; hg19: chr5-178410151; COSMIC: COSV51448660; COSMIC: COSV51448660;