NM_001006630.2:c.-124-50094C>T

Variant names:

• chr7-136942093-C-T
• rs17168817
• NM_001006630.2:c.-124-50094C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001006630.2(CHRM2):​c.-124-50094C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 152,158 control chromosomes in the GnomAD database, including 118 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 0.033 (118 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 2 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=-0.91).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.033 (5027/152158) while in subpopulation AMR AF = 0.0479 (732/15278). AF 95% confidence interval is 0.0457. There are 118 homozygotes in GnomAd4. There are 2319 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 118 gene

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.-124-50094C>T		intron	N/A	NP_001006631.1
	CHRM2	NM_000739.3		c.-124-50094C>T		intron	N/A	NP_000730.1
	CHRM2	NM_001006626.3		c.-202-8910C>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.-124-50094C>T		intron	N/A	ENSP00000505686.1
	CHRM2	ENST00000320658.9	TSL:1	c.-47+72675C>T		intron	N/A	ENSP00000319984.5
	CHRM2	ENST00000401861.1	TSL:1	c.-202-8910C>T		intron	N/A	ENSP00000384401.1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5029 AN: 152040 Hom.: 118 Cov.: 32

Gnomad AFR AF: 0.00997

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.0269

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

GnomAD4 genome AF: 0.0330 AC: 5027 AN: 152158 Hom.: 118 Cov.: 32 AF XY: 0.0312 AC XY: 2319 AN XY: 74380

African (AFR) AF: 0.00995 AC: 413 AN: 41526

American (AMR) AF: 0.0479 AC: 732 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4810

European-Finnish (FIN) AF: 0.0352 AC: 373 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0470 AC: 3197 AN: 67996

Other (OTH) AF: 0.0267 AC: 56 AN: 2100

Alfa AF: 0.0485 Hom.: 44

Bravo AF: 0.0335

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.57
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

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: rs17168817; hg19: chr7-136626840;