7-136996054-A-G

Position:

• chr7-136996054-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-47+3790A>G		intron_variant		ENST00000680005.1	NP_001006631.1
LOC349160	NR_046103.1	n.341+36740T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-47+3790A>G		intron_variant			NM_001006630.2	ENSP00000505686	P1
	ENST00000586239.5	n.273+36740T>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.638

Alfa AF: 0.646 Hom.: 12894

Bravo AF: 0.593

Asia WGS AF: 0.491 AC: 1687 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.69

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: rs6948054; hg19: chr7-136680801;