7-136995240-C-T

Variant names:

• chr7-136995240-C-T
• rs324632
• NM_001006630.2:c.-47+2976C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006630.2(CHRM2):​c.-47+2976C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,042 control chromosomes in the GnomAD database, including 58,948 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 0.88 (58948 hom., cov: 30)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 1 publications found

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]

ENSG00000234352 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006630.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-47+2976C>T		intron	N/A	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.-47+2976C>T		intron	N/A	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.-47+2976C>T		intron	N/A	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-47+2976C>T		intron	N/A	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.-46-19580C>T		intron	N/A	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.-47+2976C>T		intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133178 AN: 151922 Hom.: 58928 Cov.: 30

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.876 AC: 133239 AN: 152042 Hom.: 58948 Cov.: 30 AF XY: 0.876 AC XY: 65113 AN XY: 74310

African (AFR) AF: 0.819 AC: 33965 AN: 41464

American (AMR) AF: 0.751 AC: 11450 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3351 AN: 3472

East Asian (EAS) AF: 0.702 AC: 3609 AN: 5144

South Asian (SAS) AF: 0.832 AC: 4012 AN: 4820

European-Finnish (FIN) AF: 0.968 AC: 10248 AN: 10592

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.936 AC: 63607 AN: 67992

Other (OTH) AF: 0.880 AC: 1857 AN: 2110

Alfa AF: 0.915 Hom.: 12978

Bravo AF: 0.854

Asia WGS AF: 0.781 AC: 2702 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.86
PhyloP100		-0.077
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs324632; hg19: chr7-136679987;