rs17168817

chr7-136942093-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001006630.2(CHRM2):c.-124-50094C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 152,158 control chromosomes in the GnomAD database, including 118 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 0.033 (118 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.91).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.033 (5027/152158) while in subpopulation AMR AF= 0.0479 (732/15278). AF 95% confidence interval is 0.0457. There are 118 homozygotes in gnomad4. There are 2319 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 118 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-124-50094C>T		intron_variant		ENST00000680005.1
LOC349160	NR_046103.1	n.342-40092G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-50094C>T		intron_variant			NM_001006630.2	P1
	ENST00000586239.5	n.273+90701G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5029 AN: 152040 Hom.: 118 Cov.: 32

Gnomad AFR AF: 0.00997

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.0269

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

GnomAD4 genome AF: 0.0330 AC: 5027 AN: 152158 Hom.: 118 Cov.: 32 AF XY: 0.0312 AC XY: 2319 AN XY: 74380

Gnomad4 AFR AF: 0.00995

Gnomad4 AMR AF: 0.0479

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0352

Gnomad4 NFE AF: 0.0470

Gnomad4 OTH AF: 0.0267

Alfa AF: 0.0485 Hom.: 44

Bravo AF: 0.0335

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.24
Dann	Benign	0.57

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: rs17168817; hg19: chr7-136626840;