7-136950870-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001006630.2(CHRM2):c.-124-41317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,068 control chromosomes in the GnomAD database, including 31,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31326 hom., cov: 31)
  • Exomes 𝑓: 0.58 (40 hom.)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.627

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 7-136950870-C-T is Benign according to our data. Variant chr7-136950870-C-T is described in ClinVar as [Benign]. Clinvar id is 1226056.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-124-41317C>T		intron_variant		ENST00000680005.1
LOC349160	NR_046103.1	n.342-48869G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-41317C>T		intron_variant			NM_001006630.2	P1
	ENST00000586239.5	n.273+81924G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96699 AN: 151706 Hom.: 31292 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.634

GnomAD4 exome AF: 0.583 AC: 141 AN: 242 Hom.: 40 AF XY: 0.572 AC XY: 111 AN XY: 194

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.637 AC: 96781 AN: 151826 Hom.: 31326 Cov.: 31 AF XY: 0.633 AC XY: 46954 AN XY: 74212

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.638

Alfa AF: 0.632 Hom.: 5216

Bravo AF: 0.627

Asia WGS AF: 0.495 AC: 1720 AN: 3478

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

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.57
Dann	Benign	0.31

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: rs6960707; hg19: chr7-136635617;