7-136950254-C-T

Variant names:

• chr7-136950254-C-T
• rs1378646
• NM_001006630.2:c.-124-41933C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006630.2(CHRM2):​c.-124-41933C>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 151,976 control chromosomes in the GnomAD database, including 34,685 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 (34685 hom., cov: 31)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-41933C>T		intron_variant	Intron 2 of 3	ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-41933C>T		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101463 AN: 151858 Hom.: 34646 Cov.: 31

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.668 AC: 101549 AN: 151976 Hom.: 34685 Cov.: 31 AF XY: 0.663 AC XY: 49221 AN XY: 74284

African (AFR) AF: 0.780 AC: 32317 AN: 41446

American (AMR) AF: 0.526 AC: 8020 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2299 AN: 3468

East Asian (EAS) AF: 0.459 AC: 2364 AN: 5146

South Asian (SAS) AF: 0.486 AC: 2341 AN: 4818

European-Finnish (FIN) AF: 0.672 AC: 7091 AN: 10556

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.662 AC: 44988 AN: 67968

Other (OTH) AF: 0.661 AC: 1395 AN: 2112

Alfa AF: 0.657 Hom.: 67525

Bravo AF: 0.661

Asia WGS AF: 0.508 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.38
DANN	Benign	0.82
PhyloP100		-0.024
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1378646; hg19: chr7-136635001;