rs35916399

Variant names:

• chr7-136868746-GCACACACACACACACA-G
• rs35916399
• NM_001006630.2:c.-516_-501delCACACACACACACACA

Your query was ambiguous. Multiple possible variants found:

• chr7-136868746-GCACACACACACACACA-G
• chr7-136868746-GCACACACACACACACA-GCA
• chr7-136868746-GCACACACACACACACA-GCACA
• chr7-136868746-GCACACACACACACACA-GCACACA
• chr7-136868746-GCACACACACACACACA-GCACACACA
• chr7-136868746-GCACACACACACACACA-GCACACACACA
• chr7-136868746-GCACACACACACACACA-GCACACACACACA
• chr7-136868746-GCACACACACACACACA-GCACACACACACACA
• chr7-136868746-GCACACACACACACACA-GCACACACACACACACACA
• chr7-136868746-GCACACACACACACACA-GCACACACACACACACACACA
• chr7-136868746-GCACACACACACACACA-GCACACACACACACACACACACA
• chr7-136868746-GCACACACACACACACA-GCACACACACACACACACACACACA
• chr7-136868746-GCACACACACACACACA-GCACACACACACACACACACACACACA
• chr7-136868746-GCACACACACACACACA-GCACACACACACACACACACACACACACA
• chr7-136868746-GCACACACACACACACA-GCACACACACACACACACACACACACACACA

Variant summary

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

The NM_001006630.2(CHRM2):​c.-516_-501delCACACACACACACACA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 149,562 control chromosomes in the GnomAD database, including 516 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (516 hom., cov: 0)
  • Exomes 𝑓: 0.015 (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-GCACACACACACACACA-G is Benign according to our data. Variant chr7-136868746-GCACACACACACACACA-G is described in ClinVar as Benign. ClinVar VariationId is 1271139.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 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.-516_-501delCACACACACACACACA		5_prime_UTR	Exon 1 of 4	NP_001006631.1	P08172
	CHRM2	NM_001006627.3		c.-438_-423delCACACACACACACACA		5_prime_UTR	Exon 1 of 3	NP_001006628.1	A4D1Q0
	CHRM2	NM_001378972.1		c.-628_-613delCACACACACACACACA		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.-516_-501delCACACACACACACACA		5_prime_UTR	Exon 1 of 4	ENSP00000505686.1	P08172
	CHRM2	ENST00000445907.6	TSL:1	c.-438_-423delCACACACACACACACA		5_prime_UTR	Exon 1 of 3	ENSP00000399745.2	P08172
	ENSG00000234352	ENST00000439694.6	TSL:1	n.656-82871_656-82856delTGTGTGTGTGTGTGTG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11016 AN: 149262 Hom.: 515 Cov.: 0

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.000607

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0823

GnomAD4 exome AF: 0.0155 AC: 3 AN: 194 Hom.: 0 AF XY: 0.0185 AC XY: 3 AN XY: 162

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: 0.0174 AC: 3 AN: 172

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.0738 AC: 11018 AN: 149368 Hom.: 516 Cov.: 0 AF XY: 0.0713 AC XY: 5192 AN XY: 72794

African (AFR) AF: 0.0228 AC: 931 AN: 40808

American (AMR) AF: 0.0653 AC: 981 AN: 15030

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 356 AN: 3434

East Asian (EAS) AF: 0.000609 AC: 3 AN: 4928

South Asian (SAS) AF: 0.0730 AC: 342 AN: 4682

European-Finnish (FIN) AF: 0.0762 AC: 770 AN: 10102

Middle Eastern (MID) AF: 0.146 AC: 41 AN: 280

European-Non Finnish (NFE) AF: 0.109 AC: 7286 AN: 67118

Other (OTH) AF: 0.0814 AC: 169 AN: 2076

Alfa AF: 0.0383 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;