rs6967953

chr7-137018629-T-C

Variant summary

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

The NM_001006630.2(CHRM2):c.*2363T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,628 control chromosomes in the GnomAD database, including 27,837 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 0.59 (27835 hom., cov: 31)
  • Exomes 𝑓: 0.56 (2 hom.)
• Consequence: CHRM2 NM_001006630.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.*2363T>C		3_prime_UTR_variant	4/4	ENST00000680005.1
LOC349160	NR_046103.1	n.341+14165A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.*2363T>C		3_prime_UTR_variant	4/4		NM_001006630.2	P1
	ENST00000586239.5	n.273+14165A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89545 AN: 151490 Hom.: 27806 Cov.: 31

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.556 AC: 10 AN: 18 Hom.: 2 Cov.: 0 AF XY: 0.625 AC XY: 10 AN XY: 16

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.643

GnomAD4 genome AF: 0.591 AC: 89611 AN: 151610 Hom.: 27835 Cov.: 31 AF XY: 0.584 AC XY: 43214 AN XY: 74058

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.590

Alfa AF: 0.592 Hom.: 44767

Bravo AF: 0.584

Asia WGS AF: 0.255 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.6
Dann	Benign	0.52

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: rs6967953; hg19: chr7-136703376;