rs6963819

Positions:

• chr7-136903362-G-A

Variant summary

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

The NM_001006630.2(CHRM2):​c.-125+33944G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 389,704 control chromosomes in the GnomAD database, including 78,900 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 0.66 (34206 hom., cov: 31)
  • Exomes 𝑓: 0.61 (44694 hom.)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-125+33944G>A		intron_variant		ENST00000680005.1
LOC349160	NR_046103.1	n.342-1361C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-125+33944G>A		intron_variant			NM_001006630.2	P1
	ENST00000586239.5	n.274-117471C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100724 AN: 151742 Hom.: 34151 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.647

GnomAD4 exome AF: 0.607 AC: 144340 AN: 237844 Hom.: 44694 Cov.: 0 AF XY: 0.605 AC XY: 81623 AN XY: 134996

Gnomad4 AFR exome AF: 0.772

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.651

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.636

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.664 AC: 100828 AN: 151860 Hom.: 34206 Cov.: 31 AF XY: 0.660 AC XY: 48988 AN XY: 74222

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.650

Alfa AF: 0.640 Hom.: 48961

Bravo AF: 0.656

Asia WGS AF: 0.551 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.18

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: rs6963819; hg19: chr7-136588109; COSMIC: COSV57766314; COSMIC: COSV57766314;