rs10271552

Positions:

• chr7-136939912-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.-124-52275T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,180 control chromosomes in the GnomAD database, including 2,887 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 0.16 (2887 hom., cov: 33)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-52275T>C		intron_variant		ENST00000680005.1	NP_001006631.1
LOC349160	NR_046103.1	n.342-37911A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-52275T>C		intron_variant			NM_001006630.2	ENSP00000505686	P1
	ENST00000586239.5	n.273+92882A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24515 AN: 152062 Hom.: 2876 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.131

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.161 AC: 24552 AN: 152180 Hom.: 2887 Cov.: 33 AF XY: 0.159 AC XY: 11822 AN XY: 74406

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.0895

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0359

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.129

Alfa AF: 0.117 Hom.: 1301

Bravo AF: 0.168

Asia WGS AF: 0.0420 AC: 147 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.64

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: rs10271552; hg19: chr7-136624659;