rs773330734

Variant names:

• chr7-137015838-A-T
• rs773330734
• NM_001006630.2:c.973A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-137015838-A-T
• chr7-137015838-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001006630.2(CHRM2):​c.973A>T​(p.Ile325Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000973 in 1,612,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: CHRM2 NM_001006630.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 6.32
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23122257).

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.973A>T	p.Ile325Phe	missense	Exon 4 of 4	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.973A>T	p.Ile325Phe	missense	Exon 4 of 4	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.973A>T	p.Ile325Phe	missense	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.973A>T	p.Ile325Phe	missense	Exon 4 of 4	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.973A>T	p.Ile325Phe	missense	Exon 3 of 3	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.973A>T	p.Ile325Phe	missense	Exon 5 of 5	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 151944 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000320 AC: 8 AN: 250234 AF XY: 0.0000296

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000620

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 148 AN: 1460970 Hom.: 0 Cov.: 31 AF XY: 0.0000936 AC XY: 68 AN XY: 726792

African (AFR) AF: 0.0000299 AC: 1 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1111416

Other (OTH) AF: 0.000249 AC: 15 AN: 60344

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 151944 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74214

African (AFR) AF: 0.0000242 AC: 1 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67930

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000676 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.021
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.16
Sift	Benign	0.21	T
Sift4G	Benign	0.55	T
Polyphen		0.025	B
Vest4		0.40
MVP		0.86
MPC		0.90
ClinPred		0.10	T
GERP RS		5.4
Varity_R		0.17
gMVP		0.52
Mutation Taster		=6/94	disease causing

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: rs773330734; hg19: chr7-136700585;