7-136950870-C-T

Variant names:

• chr7-136950870-C-T
• rs6960707
• NM_001006630.2:c.-124-41317C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001006630.2(CHRM2):​c.-124-41317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,068 control chromosomes in the GnomAD database, including 31,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31326 hom., cov: 31)
  • Exomes 𝑓: 0.58 (40 hom.)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.627
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 7-136950870-C-T is Benign according to our data. Variant chr7-136950870-C-T is described in ClinVar as Benign. ClinVar VariationId is 1226056.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-124-41317C>T		intron	N/A	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.-124-41317C>T		intron	N/A	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.-202-133C>T		intron	N/A	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-124-41317C>T		intron	N/A	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.-46-63950C>T		intron	N/A	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.-202-133C>T		intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96699 AN: 151706 Hom.: 31292 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.634

GnomAD4 exome AF: 0.583 AC: 141 AN: 242 Hom.: 40 AF XY: 0.572 AC XY: 111 AN XY: 194

African (AFR) AF: 0.750 AC: 6 AN: 8

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.200 AC: 2 AN: 10

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.590 AC: 118 AN: 200

Other (OTH) AF: 0.667 AC: 8 AN: 12

GnomAD4 genome AF: 0.637 AC: 96781 AN: 151826 Hom.: 31326 Cov.: 31 AF XY: 0.633 AC XY: 46954 AN XY: 74212

African (AFR) AF: 0.681 AC: 28174 AN: 41378

American (AMR) AF: 0.516 AC: 7866 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2293 AN: 3472

East Asian (EAS) AF: 0.445 AC: 2284 AN: 5134

South Asian (SAS) AF: 0.481 AC: 2315 AN: 4808

European-Finnish (FIN) AF: 0.663 AC: 6981 AN: 10534

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44792 AN: 67938

Other (OTH) AF: 0.638 AC: 1344 AN: 2108

Alfa AF: 0.632 Hom.: 5216

Bravo AF: 0.627

Asia WGS AF: 0.495 AC: 1720 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.31
PhyloP100		-0.63
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: rs6960707; hg19: chr7-136635617;