7-136950783-C-CTGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency: Genomes: 𝑓 0.17 (2426 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-C-CTGT is Benign according to our data. Variant chr7-136950783-C-CTGT is described in ClinVar as [Benign]. Clinvar id is 1178961.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-124-41360_-124-41358dup		intron_variant		ENST00000680005.1
LOC349160	NR_046103.1	n.342-48783_342-48782insACA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-41360_-124-41358dup		intron_variant			NM_001006630.2	P1
	ENST00000586239.5	n.273+82010_273+82011insACA		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.166 AC: 24786 AN: 149012 Hom.: 2421 Cov.: 16

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.166 AC: 24801 AN: 149118 Hom.: 2426 Cov.: 16 AF XY: 0.170 AC XY: 12327 AN XY: 72610

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.171

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

Feb 03, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

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;