7-136950783-CTGT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001006630.2(CHRM2):c.-124-41360_-124-41358del 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 16. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 61 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-124-41360_-124-41358del		intron_variant		ENST00000680005.1
LOC349160	NR_046103.1	n.342-48785_342-48783del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-41360_-124-41358del		intron_variant			NM_001006630.2	P1
	ENST00000586239.5	n.273+82008_273+82010del		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.0304

Gnomad4 AMR AF: 0.0283

Gnomad4 ASJ AF: 0.0344

Gnomad4 EAS AF: 0.0281

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0589

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.0288

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs200954535; hg19: chr7-136635530;