7-136911710-A-G

Variant names:

• chr7-136911710-A-G
• rs7810473
• NM_001006630.2:c.-125+42292A>G

Variant summary

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

The NM_001006630.2(CHRM2):​c.-125+42292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,852 control chromosomes in the GnomAD database, including 12,758 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 0.40 (12758 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+42292A>G		intron_variant	Intron 2 of 3	ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-125+42292A>G		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60488 AN: 151732 Hom.: 12747 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.0412

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.399 AC: 60526 AN: 151852 Hom.: 12758 Cov.: 32 AF XY: 0.392 AC XY: 29070 AN XY: 74186

African (AFR) AF: 0.445 AC: 18439 AN: 41442

American (AMR) AF: 0.320 AC: 4876 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1539 AN: 3466

East Asian (EAS) AF: 0.0407 AC: 209 AN: 5138

South Asian (SAS) AF: 0.172 AC: 829 AN: 4826

European-Finnish (FIN) AF: 0.420 AC: 4433 AN: 10564

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28848 AN: 67856

Other (OTH) AF: 0.396 AC: 836 AN: 2112

Alfa AF: 0.404 Hom.: 21090

Bravo AF: 0.393

Asia WGS AF: 0.147 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.20
PhyloP100		-1.4
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: rs7810473; hg19: chr7-136596457;