chr7-136992623-T-C

Position:

• chr7-136992623-T-C

Variant summary

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

The NM_001006630.2(CHRM2):​c.-47+359T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,042 control chromosomes in the GnomAD database, including 32,974 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 0.65 (32974 hom., cov: 33)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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]

ENSG00000234352 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-47+359T>C		intron_variant		ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-47+359T>C		intron_variant			NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98367 AN: 151924 Hom.: 32953 Cov.: 33

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.647 AC: 98416 AN: 152042 Hom.: 32974 Cov.: 33 AF XY: 0.652 AC XY: 48424 AN XY: 74316

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.675

Alfa AF: 0.602 Hom.: 1913

Bravo AF: 0.618

Asia WGS AF: 0.509 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.030
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: rs7785096; hg19: chr7-136677370;