chr7-136950804-T-A

Position:

• chr7-136950804-T-A

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.-124-41383T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 150,922 control chromosomes in the GnomAD database, including 32,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (32133 hom., cov: 30)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.299

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=-0.95).
• BP6: Variant 7-136950804-T-A is Benign according to our data. Variant chr7-136950804-T-A is described in ClinVar as [Benign]. Clinvar id is 1224957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-41383T>A		intron_variant		ENST00000680005.1	NP_001006631.1
LOC349160	NR_046103.1	n.342-48803A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-41383T>A		intron_variant			NM_001006630.2	ENSP00000505686	P1
	ENST00000586239.5	n.273+81990A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.649 AC: 97830 AN: 150810 Hom.: 32102 Cov.: 30

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.593

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.649 AC: 97905 AN: 150922 Hom.: 32133 Cov.: 30 AF XY: 0.644 AC XY: 47477 AN XY: 73744

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.642

Alfa AF: 0.657 Hom.: 3889

Bravo AF: 0.638

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

Nov 12, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.24

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: rs28529003; hg19: chr7-136635551;