7-136868746-GCACACACACACACACA-GCACACACACA

Variant names:

• chr7-136868746-GCACACA-G
• rs35916399
• NM_001006630.2:c.-506_-501delCACACA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001006630.2(CHRM2):​c.-506_-501delCACACA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 149,490 control chromosomes in the GnomAD database, including 1,137 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1137 hom., cov: 0)
  • Exomes 𝑓: 0.036 (0 hom.)
• Consequence: CHRM2 NM_001006630.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.33
• Publications: 3 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 -10 ACMG points.

• BP6: Variant 7-136868746-GCACACA-G is Benign according to our data. Variant chr7-136868746-GCACACA-G is described in ClinVar as Benign. ClinVar VariationId is 1270234.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 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.-506_-501delCACACA		5_prime_UTR	Exon 1 of 4	NP_001006631.1	P08172
	CHRM2	NM_001006627.3		c.-428_-423delCACACA		5_prime_UTR	Exon 1 of 3	NP_001006628.1	A4D1Q0
	CHRM2	NM_001378972.1		c.-618_-613delCACACA		5_prime_UTR	Exon 1 of 5	NP_001365901.1	P08172

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-506_-501delCACACA		5_prime_UTR	Exon 1 of 4	ENSP00000505686.1	P08172
	CHRM2	ENST00000445907.6	TSL:1	c.-428_-423delCACACA		5_prime_UTR	Exon 1 of 3	ENSP00000399745.2	P08172
	ENSG00000234352	ENST00000439694.6	TSL:1	n.656-82861_656-82856delTGTGTG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.107 AC: 15904 AN: 149188 Hom.: 1135 Cov.: 0

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0920

Gnomad EAS AF: 0.00526

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0430

Gnomad MID AF: 0.0927

Gnomad NFE AF: 0.0830

Gnomad OTH AF: 0.0915

GnomAD4 exome AF: 0.0357 AC: 7 AN: 196 Hom.: 0 AF XY: 0.0305 AC XY: 5 AN XY: 164

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0345 AC: 6 AN: 174

Other (OTH) AF: 0.125 AC: 1 AN: 8

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000231804), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.107 AC: 15926 AN: 149294 Hom.: 1137 Cov.: 0 AF XY: 0.102 AC XY: 7456 AN XY: 72756

African (AFR) AF: 0.193 AC: 7858 AN: 40764

American (AMR) AF: 0.0726 AC: 1090 AN: 15022

Ashkenazi Jewish (ASJ) AF: 0.0920 AC: 316 AN: 3434

East Asian (EAS) AF: 0.00528 AC: 26 AN: 4928

South Asian (SAS) AF: 0.0408 AC: 191 AN: 4682

European-Finnish (FIN) AF: 0.0430 AC: 434 AN: 10092

Middle Eastern (MID) AF: 0.0964 AC: 27 AN: 280

European-Non Finnish (NFE) AF: 0.0830 AC: 5570 AN: 67106

Other (OTH) AF: 0.0906 AC: 188 AN: 2076

Alfa AF: 0.0259 Hom.: 771

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
PhyloP100		3.3
Mutation Taster		=297/3	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs35916399; hg19: chr7-136553493;