chr7-136904347-C-T

Variant names:

• chr7-136904347-C-T
• rs10488599
• NM_001006630.2:c.-125+34929C>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.-125+34929C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 151,778 control chromosomes in the GnomAD database, including 2,223 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 (2223 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-125+34929C>T		intron	N/A	NP_001006631.1
	CHRM2	NM_000739.3		c.-125+34929C>T		intron	N/A	NP_000730.1
	CHRM2	NM_001006626.3		c.-203+34929C>T		intron	N/A	NP_001006627.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-125+34929C>T		intron	N/A	ENSP00000505686.1
	CHRM2	ENST00000320658.9	TSL:1	c.-47+34929C>T		intron	N/A	ENSP00000319984.5
	CHRM2	ENST00000401861.1	TSL:1	c.-203+34929C>T		intron	N/A	ENSP00000384401.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24261 AN: 151660 Hom.: 2217 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.160 AC: 24287 AN: 151778 Hom.: 2223 Cov.: 32 AF XY: 0.166 AC XY: 12330 AN XY: 74164

African (AFR) AF: 0.131 AC: 5447 AN: 41468

American (AMR) AF: 0.146 AC: 2223 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 470 AN: 3468

East Asian (EAS) AF: 0.411 AC: 2108 AN: 5134

South Asian (SAS) AF: 0.314 AC: 1512 AN: 4814

European-Finnish (FIN) AF: 0.188 AC: 1984 AN: 10526

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10038 AN: 67830

Other (OTH) AF: 0.164 AC: 345 AN: 2108

Alfa AF: 0.154 Hom.: 251

Bravo AF: 0.153

Asia WGS AF: 0.361 AC: 1242 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.25
PhyloP100		-0.36
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: rs10488599; hg19: chr7-136589094; COSMIC: COSV57775353; COSMIC: COSV57775353;