chr7-136925178-C-T

Position:

• chr7-136925178-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006630.2(CHRM2):​c.-125+55760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,022 control chromosomes in the GnomAD database, including 34,618 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34618 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-125+55760C>T		intron_variant		ENST00000680005.1
LOC349160	NR_046103.1	n.342-23177G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-125+55760C>T		intron_variant			NM_001006630.2	P1
	ENST00000586239.5	n.273+107616G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101410 AN: 151904 Hom.: 34562 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.668 AC: 101515 AN: 152022 Hom.: 34618 Cov.: 32 AF XY: 0.663 AC XY: 49236 AN XY: 74294

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.659

Alfa AF: 0.657 Hom.: 44894

Bravo AF: 0.658

Asia WGS AF: 0.511 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.81
DANN	Benign	0.41

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: rs1364407; hg19: chr7-136609925;