chr7-136950783-CTGT-C

Variant names:

• chr7-136950783-CTGT-C
• rs200954535
• NM_001006630.2:c.-124-41360_-124-41358delGTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001006630.2(CHRM2):​c.-124-41360_-124-41358delGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.025 (61 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-CTGT-C is Benign according to our data. Variant chr7-136950783-CTGT-C is described in ClinVar as Benign. ClinVar VariationId is 1222026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0252 (3771/149662) while in subpopulation AFR AF = 0.0304 (1243/40910). AF 95% confidence interval is 0.029. There are 61 homozygotes in GnomAd4. There are 2011 alleles in the male GnomAd4 subpopulation. Median coverage is 16. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 61 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.-124-41360_-124-41358delGTT		intron	N/A	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.-124-41360_-124-41358delGTT		intron	N/A	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.-202-176_-202-174delGTT		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.-124-41403_-124-41401delTGT		intron	N/A	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.-46-64036_-46-64034delTGT		intron	N/A	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.-202-219_-202-217delTGT		intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3773 AN: 149556 Hom.: 61 Cov.: 16

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.0199

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.0344

Gnomad EAS AF: 0.0286

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.0673

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0296

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

GnomAD4 genome AF: 0.0252 AC: 3771 AN: 149662 Hom.: 61 Cov.: 16 AF XY: 0.0276 AC XY: 2011 AN XY: 72858

African (AFR) AF: 0.0304 AC: 1243 AN: 40910

American (AMR) AF: 0.0283 AC: 421 AN: 14888

Ashkenazi Jewish (ASJ) AF: 0.0344 AC: 119 AN: 3458

East Asian (EAS) AF: 0.0281 AC: 137 AN: 4884

South Asian (SAS) AF: 0.0172 AC: 79 AN: 4582

European-Finnish (FIN) AF: 0.0589 AC: 600 AN: 10186

Middle Eastern (MID) AF: 0.0729 AC: 21 AN: 288

European-Non Finnish (NFE) AF: 0.0159 AC: 1073 AN: 67478

Other (OTH) AF: 0.0288 AC: 60 AN: 2082

Alfa AF: 0.00699 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

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: rs200954535; hg19: chr7-136635530;