NM_001006630.2:c.-125+33678T>C

Variant names:

• chr7-136903096-T-C
• rs10488598
• NM_001006630.2:c.-125+33678T>C

Variant summary

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

The NM_001006630.2(CHRM2):​c.-125+33678T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 528,114 control chromosomes in the GnomAD database, including 18,758 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 0.22 (4969 hom., cov: 32)
  • Exomes 𝑓: 0.25 (13789 hom.)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 6 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:):

MIR490 (HGNC:32075): (microRNA 490) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006630.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-125+33678T>C		intron	N/A	NP_001006631.1
	CHRM2	NM_000739.3		c.-125+33678T>C		intron	N/A	NP_000730.1
	CHRM2	NM_001006626.3		c.-203+33678T>C		intron	N/A	NP_001006627.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-125+33678T>C		intron	N/A	ENSP00000505686.1
	CHRM2	ENST00000320658.9	TSL:1	c.-47+33678T>C		intron	N/A	ENSP00000319984.5
	CHRM2	ENST00000401861.1	TSL:1	c.-203+33678T>C		intron	N/A	ENSP00000384401.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33934 AN: 151836 Hom.: 4970 Cov.: 32

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.252 AC: 94650 AN: 376160 Hom.: 13789 Cov.: 0 AF XY: 0.245 AC XY: 52541 AN XY: 214574

African (AFR) AF: 0.0570 AC: 572 AN: 10028

American (AMR) AF: 0.178 AC: 6273 AN: 35150

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 3454 AN: 11644

East Asian (EAS) AF: 0.0460 AC: 599 AN: 13012

South Asian (SAS) AF: 0.129 AC: 8475 AN: 65606

European-Finnish (FIN) AF: 0.306 AC: 9593 AN: 31320

Middle Eastern (MID) AF: 0.295 AC: 749 AN: 2540

European-Non Finnish (NFE) AF: 0.318 AC: 60515 AN: 190430

Other (OTH) AF: 0.269 AC: 4420 AN: 16430

GnomAD4 genome AF: 0.223 AC: 33919 AN: 151954 Hom.: 4969 Cov.: 32 AF XY: 0.220 AC XY: 16372 AN XY: 74278

African (AFR) AF: 0.0613 AC: 2544 AN: 41506

American (AMR) AF: 0.228 AC: 3478 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3466

East Asian (EAS) AF: 0.0391 AC: 201 AN: 5140

South Asian (SAS) AF: 0.132 AC: 637 AN: 4824

European-Finnish (FIN) AF: 0.306 AC: 3242 AN: 10584

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21988 AN: 67880

Other (OTH) AF: 0.255 AC: 537 AN: 2102

Alfa AF: 0.285 Hom.: 3524

Bravo AF: 0.209

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.81
PhyloP100		-1.2
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: rs10488598; hg19: chr7-136587843;