7-136950783-CTGTTGTTGTTGTTGTTGTTGTTGTTGT-CTGTTGTTGTTGTTGTTGTTGTTGTTGTTGTTGT

Variant names:

• chr7-136950783-C-CTGTTGT
• rs200954535
• NM_001006630.2:c.-124-41363_-124-41358dupGTTGTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001006630.2(CHRM2):​c.-124-41363_-124-41358dupGTTGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.092 (724 hom., cov: 16)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.190
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 7-136950783-C-CTGTTGT is Benign according to our data. Variant chr7-136950783-C-CTGTTGT is described in ClinVar as Benign. ClinVar VariationId is 1240542.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-124-41363_-124-41358dupGTTGTT		intron	N/A	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.-124-41363_-124-41358dupGTTGTT		intron	N/A	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.-202-179_-202-174dupGTTGTT		intron	N/A	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-124-41404_-124-41403insTGTTGT		intron	N/A	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.-46-64037_-46-64036insTGTTGT		intron	N/A	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.-202-220_-202-219insTGTTGT		intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes AF: 0.0925 AC: 13811 AN: 149314 Hom.: 724 Cov.: 16

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.0876

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.0994

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0877

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

GnomAD4 genome AF: 0.0925 AC: 13820 AN: 149422 Hom.: 724 Cov.: 16 AF XY: 0.0899 AC XY: 6539 AN XY: 72774

African (AFR) AF: 0.0468 AC: 1911 AN: 40870

American (AMR) AF: 0.101 AC: 1498 AN: 14864

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 299 AN: 3456

East Asian (EAS) AF: 0.0874 AC: 426 AN: 4876

South Asian (SAS) AF: 0.102 AC: 467 AN: 4568

European-Finnish (FIN) AF: 0.0737 AC: 752 AN: 10198

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 290

European-Non Finnish (NFE) AF: 0.121 AC: 8160 AN: 67320

Other (OTH) AF: 0.0868 AC: 180 AN: 2074

Alfa AF: 0.0389 Hom.: 75

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200954535; hg19: chr7-136635530; COSMIC: COSV57785072;