rs148163637

Variant names:

• chr7-137015321-C-T
• rs148163637
• NM_001006630.2:c.456C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001006630.2(CHRM2):​c.456C>T​(p.Phe152Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000545 in 1,613,396 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (7 hom.)
• Consequence: CHRM2 NM_001006630.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.714
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 7-137015321-C-T is Benign according to our data. Variant chr7-137015321-C-T is described in ClinVar as Benign. ClinVar VariationId is 478115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.714 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.456C>T	p.Phe152Phe	synonymous	Exon 4 of 4	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.456C>T	p.Phe152Phe	synonymous	Exon 4 of 4	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.456C>T	p.Phe152Phe	synonymous	Exon 5 of 5	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.456C>T	p.Phe152Phe	synonymous	Exon 4 of 4	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.456C>T	p.Phe152Phe	synonymous	Exon 3 of 3	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.456C>T	p.Phe152Phe	synonymous	Exon 5 of 5	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes AF: 0.000632 AC: 96 AN: 151970 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00141 AC: 352 AN: 249570 AF XY: 0.00145

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0145

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000624

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000537 AC: 784 AN: 1461306 Hom.: 7 Cov.: 31 AF XY: 0.000616 AC XY: 448 AN XY: 726968

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.000985 AC: 44 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0128 AC: 509 AN: 39656

South Asian (SAS) AF: 0.00137 AC: 118 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.0000657 AC: 73 AN: 1111702

Other (OTH) AF: 0.000597 AC: 36 AN: 60352

GnomAD4 genome AF: 0.000631 AC: 96 AN: 152090 Hom.: 0 Cov.: 32 AF XY: 0.000821 AC XY: 61 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41536

American (AMR) AF: 0.000131 AC: 2 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0148 AC: 76 AN: 5122

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67950

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000123 Hom.: 0

Bravo AF: 0.000903

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Dilated Cardiomyopathy, Dominant (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.8
DANN	Benign	0.65
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148163637; hg19: chr7-136700068; COSMIC: COSV57765700;