3-6773301-C-T

Variant names:

• chr3-6773301-C-T
• rs6781770
• ENST00000448328.6:c.-180+3183C>T

Variant summary

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

The ENST00000448328.6(GRM7):​c.-180+3183C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,399,068 control chromosomes in the GnomAD database, including 134,727 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 0.40 (13467 hom., cov: 31)
  • Exomes 𝑓: 0.44 (121260 hom.)
• Consequence: GRM7 ENST00000448328.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• Publications: 3 publications found

Genes affected

GRM7 (HGNC:4599): (glutamate metabotropic receptor 7) L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it 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 three 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

MRPS36P1 (HGNC:29771): (mitochondrial ribosomal protein S36 pseudogene 1)

GRM7-AS3 (HGNC:42444): (GRM7 antisense RNA 3)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448328.6. 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
	GRM7-AS3	NR_110123.1		n.150+17752G>A		intron	N/A
	GRM7-AS3	NR_110125.1		n.150+17752G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000448328.6	TSL:4	c.-180+3183C>T		intron	N/A	ENSP00000393799.2	C9JU97
	MRPS36P1	ENST00000421291.1	TSL:6	n.43G>A		non_coding_transcript_exon	Exon 1 of 1
	GRM7-AS3	ENST00000412629.7	TSL:3	n.184+17752G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61062 AN: 151836 Hom.: 13469 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.436 AC: 543971 AN: 1247112 Hom.: 121260 Cov.: 23 AF XY: 0.439 AC XY: 277073 AN XY: 630642

African (AFR) AF: 0.197 AC: 5975 AN: 30338

American (AMR) AF: 0.417 AC: 18410 AN: 44178

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 11623 AN: 24666

East Asian (EAS) AF: 0.616 AC: 23612 AN: 38324

South Asian (SAS) AF: 0.399 AC: 32787 AN: 82134

European-Finnish (FIN) AF: 0.439 AC: 23153 AN: 52792

Middle Eastern (MID) AF: 0.513 AC: 2734 AN: 5334

European-Non Finnish (NFE) AF: 0.439 AC: 402605 AN: 916406

Other (OTH) AF: 0.436 AC: 23072 AN: 52940

GnomAD4 genome AF: 0.402 AC: 61072 AN: 151956 Hom.: 13467 Cov.: 31 AF XY: 0.404 AC XY: 29994 AN XY: 74246

African (AFR) AF: 0.216 AC: 8958 AN: 41470

American (AMR) AF: 0.459 AC: 7006 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3468

East Asian (EAS) AF: 0.597 AC: 3070 AN: 5140

South Asian (SAS) AF: 0.414 AC: 1986 AN: 4800

European-Finnish (FIN) AF: 0.431 AC: 4543 AN: 10544

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32337 AN: 67950

Other (OTH) AF: 0.443 AC: 934 AN: 2108

Alfa AF: 0.407 Hom.: 2526

Bravo AF: 0.393

Asia WGS AF: 0.497 AC: 1729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		0.63

Splicing

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

Other links and lift over

dbSNP: rs6781770; hg19: chr3-6814988;