7-136996054-A-G

Variant names:

• chr7-136996054-A-G
• rs6948054
• NM_001006630.2:c.-47+3790A>G

Variant summary

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

The NM_001006630.2(CHRM2):​c.-47+3790A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,650 control chromosomes in the GnomAD database, including 29,767 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 0.62 (29767 hom., cov: 32)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• 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:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 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.-47+3790A>G		intron	N/A	NP_001006631.1
	CHRM2	NM_000739.3		c.-47+3790A>G		intron	N/A	NP_000730.1
	CHRM2	NM_001006626.3		c.-47+3790A>G		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.-47+3790A>G		intron	N/A	ENSP00000505686.1
	CHRM2	ENST00000320658.9	TSL:1	c.-46-18766A>G		intron	N/A	ENSP00000319984.5
	CHRM2	ENST00000401861.1	TSL:1	c.-47+3790A>G		intron	N/A	ENSP00000384401.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93668 AN: 151532 Hom.: 29748 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.618 AC: 93717 AN: 151650 Hom.: 29767 Cov.: 32 AF XY: 0.622 AC XY: 46068 AN XY: 74118

African (AFR) AF: 0.537 AC: 22244 AN: 41436

American (AMR) AF: 0.535 AC: 8153 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2489 AN: 3472

East Asian (EAS) AF: 0.377 AC: 1943 AN: 5150

South Asian (SAS) AF: 0.535 AC: 2577 AN: 4816

European-Finnish (FIN) AF: 0.780 AC: 8109 AN: 10392

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46113 AN: 67834

Other (OTH) AF: 0.638 AC: 1346 AN: 2110

Alfa AF: 0.649 Hom.: 14622

Bravo AF: 0.593

Asia WGS AF: 0.491 AC: 1687 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.69
PhyloP100		-1.4
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: rs6948054; hg19: chr7-136680801;