7-136869413-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001006630.2(CHRM2):c.-130C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 152,410 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (179 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (0 hom.)
• Consequence: CHRM2 NM_001006630.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.339

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 7-136869413-C-T is Benign according to our data. Variant chr7-136869413-C-T is described in ClinVar as [Benign]. Clinvar id is 384814.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-130C>T		5_prime_UTR_variant	2/4	ENST00000680005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-130C>T		5_prime_UTR_variant	2/4		NM_001006630.2	P1
	ENST00000586239.5	n.274-83522G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3248 AN: 152090 Hom.: 182 Cov.: 32

Gnomad AFR AF: 0.00364

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00454

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.00495 AC: 1 AN: 202 Hom.: 0 Cov.: 0 AF XY: 0.00595 AC XY: 1 AN XY: 168

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00556

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0213 AC: 3242 AN: 152208 Hom.: 179 Cov.: 32 AF XY: 0.0263 AC XY: 1957 AN XY: 74420

Gnomad4 AFR AF: 0.00363

Gnomad4 AMR AF: 0.0534

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.0211

Gnomad4 NFE AF: 0.00454

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00598 Hom.: 3

Bravo AF: 0.0207

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 19, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	7.6
Dann	Benign	0.90

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: rs77128879; hg19: chr7-136554160; COSMIC: COSV57778717;