chr7-136939573-C-A

Position:

• chr7-136939573-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006630.2(CHRM2):​c.-124-52614C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,068 control chromosomes in the GnomAD database, including 20,992 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 0.51 (20992 hom., cov: 33)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.949

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-124-52614C>A		intron_variant		ENST00000680005.1	NP_001006631.1
LOC349160	NR_046103.1	n.342-37572G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-124-52614C>A		intron_variant			NM_001006630.2	ENSP00000505686	P1
	ENST00000586239.5	n.273+93221G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77075 AN: 151950 Hom.: 20962 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.0414

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.507 AC: 77138 AN: 152068 Hom.: 20992 Cov.: 33 AF XY: 0.497 AC XY: 36942 AN XY: 74334

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.0409

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.500

Alfa AF: 0.494 Hom.: 27684

Bravo AF: 0.507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.5
DANN	Benign	0.53

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: rs7800170; hg19: chr7-136624320;