ENST00000439694.5:n.343+11501T>C

Variant names:

• chr7-137020404-A-G
• rs1378650
• ENST00000439694.5:n.343+11501T>C

Variant summary

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

The ENST00000439694.5(ENSG00000234352):​n.343+11501T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,582 control chromosomes in the GnomAD database, including 23,050 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 0.54 (23049 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: ENSG00000234352 ENST00000439694.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391

Genes affected

ENSG00000234352 (HGNC:):

CHRM2 (HGNC:1951): (cholinergic receptor muscarinic 2) The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine to these receptors and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The muscarinic cholinergic receptor 2 is involved in mediation of bradycardia and a decrease in cardiac contractility. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.*4138A>G		downstream_gene_variant		ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.*4138A>G		downstream_gene_variant			NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81404 AN: 151462 Hom.: 23023 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.541

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 AF XY: 1.00 AC XY: 2 AN XY: 2

GnomAD4 genome AF: 0.537 AC: 81465 AN: 151580 Hom.: 23049 Cov.: 31 AF XY: 0.532 AC XY: 39396 AN XY: 74040

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.535

Alfa AF: 0.445 Hom.: 1772

Bravo AF: 0.527

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1378650; hg19: chr7-136705151;