7-136950783-CTGTTGTTGTTGTTGTTGTTGTTGTTGT-CTGTTGTTGTTGTTGTTGTTGTTGTTGTTGTTGTTGT

Variant names:

• chr7-136950783-C-CTGTTGTTGT
• rs200954535
• NM_001006630.2:c.-124-41366_-124-41358dupGTTGTTGTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001006630.2(CHRM2):​c.-124-41366_-124-41358dupGTTGTTGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0057 (6 hom., cov: 16)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 6 gene

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.-124-41366_-124-41358dupGTTGTTGTT		intron	N/A	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.-124-41366_-124-41358dupGTTGTTGTT		intron	N/A	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.-202-182_-202-174dupGTTGTTGTT		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.-124-41404_-124-41403insTGTTGTTGT		intron	N/A	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.-46-64037_-46-64036insTGTTGTTGT		intron	N/A	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.-202-220_-202-219insTGTTGTTGT		intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes AF: 0.00575 AC: 861 AN: 149642 Hom.: 6 Cov.: 16

Gnomad AFR AF: 0.00618

Gnomad AMI AF: 0.00221

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00780

Gnomad EAS AF: 0.00756

Gnomad SAS AF: 0.00480

Gnomad FIN AF: 0.000685

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00625

Gnomad OTH AF: 0.00679

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

GnomAD4 genome AF: 0.00575 AC: 861 AN: 149748 Hom.: 6 Cov.: 16 AF XY: 0.00565 AC XY: 412 AN XY: 72924

African (AFR) AF: 0.00616 AC: 252 AN: 40922

American (AMR) AF: 0.00517 AC: 77 AN: 14902

Ashkenazi Jewish (ASJ) AF: 0.00780 AC: 27 AN: 3462

East Asian (EAS) AF: 0.00758 AC: 37 AN: 4884

South Asian (SAS) AF: 0.00480 AC: 22 AN: 4584

European-Finnish (FIN) AF: 0.000685 AC: 7 AN: 10218

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00625 AC: 422 AN: 67496

Other (OTH) AF: 0.00672 AC: 14 AN: 2084

Alfa AF: 0.00124 Hom.: 75

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs200954535;

hg19: chr7-136635530;