7-136869276-G-A

Variant names:

• chr7-136869276-G-A
• rs139124053
• NM_001006630.2:c.-267G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001006630.2(CHRM2):​c.-267G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00653 in 152,590 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (0 hom.)
• Consequence: CHRM2 NM_001006630.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.610

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-136869276-G-A is Benign according to our data. Variant chr7-136869276-G-A is described in ClinVar as [Benign]. Clinvar id is 384721.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-267G>A		5_prime_UTR_variant	Exon 2 of 4	ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005	c.-267G>A		5_prime_UTR_variant	Exon 2 of 4		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.00654 AC: 996 AN: 152184 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00657

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00694 AC: 2 AN: 288 Hom.: 0 Cov.: 0 AF XY: 0.00952 AC XY: 2 AN XY: 210

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00820

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00653 AC: 995 AN: 152302 Hom.: 7 Cov.: 32 AF XY: 0.00606 AC XY: 451 AN XY: 74468

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00659

Gnomad4 SAS AF: 0.00393

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00662 Hom.: 1

Bravo AF: 0.00693

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 26, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.79
CADD	Benign	9.9
DANN	Benign	0.88

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: rs139124053; hg19: chr7-136554023;