rs6962027

chr7-137017188-T-Achr7-137017188-T-G

Variant summary

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

The NM_001006630.2(CHRM2):c.*922T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,792 control chromosomes in the GnomAD database, including 27,643 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 0.58 (27643 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CHRM2 NM_001006630.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.*922T>A		3_prime_UTR_variant	4/4	ENST00000680005.1
LOC349160	NR_046103.1	n.341+15606A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.*922T>A		3_prime_UTR_variant	4/4		NM_001006630.2	P1
	ENST00000586239.5	n.273+15606A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88110 AN: 151670 Hom.: 27598 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.581 AC: 88199 AN: 151790 Hom.: 27643 Cov.: 32 AF XY: 0.574 AC XY: 42567 AN XY: 74148

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.568

Alfa AF: 0.451 Hom.: 1318

Bravo AF: 0.580

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	3.7
Dann	Benign	0.70

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: rs6962027; hg19: chr7-136701935;