rs10488598

Positions:

• chr7-136903096-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.-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

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=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+33678T>C		intron_variant		ENST00000680005.1	NP_001006631.1
LOC349160	NR_046103.1	n.342-1095A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-125+33678T>C		intron_variant			NM_001006630.2	ENSP00000505686	P1
	ENST00000586239.5	n.274-117205A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.0570

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.0460

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.269

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

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.0391

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.255

Alfa AF: 0.286 Hom.: 3168

Bravo AF: 0.209

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.81

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: rs10488598; hg19: chr7-136587843;