NM_001375978.1:c.-312-10359C>T

Variant names:

• chr1-239621865-C-T
• rs2355230
• NM_001375978.1:c.-312-10359C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001375978.1(CHRM3):​c.-312-10359C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 143,264 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000070 (0 hom., cov: 28)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 4 publications found

Genes affected

CHRM3 (HGNC:1952): (cholinergic receptor muscarinic 3) 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 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 3 controls smooth muscle contraction and its stimulation causes secretion of glandular tissue. Alternative promoter use and alternative splicing results in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]

CHRM3 Gene-Disease associations (from GenCC):

• prune belly syndrome

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

LOC105373225 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375978.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM3	NM_001375978.1	MANE Select	c.-312-10359C>T		intron	N/A	NP_001362907.1
	CHRM3	NM_001347716.2		c.-541-10359C>T		intron	N/A	NP_001334645.1
	CHRM3	NM_001375979.1		c.-249-56321C>T		intron	N/A	NP_001362908.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM3	ENST00000676153.1	MANE Select	c.-312-10359C>T		intron	N/A	ENSP00000502667.1
	CHRM3	ENST00000615928.5	TSL:5	c.-312-10359C>T		intron	N/A	ENSP00000482377.1
	CHRM3	ENST00000675184.1		c.-312-10359C>T		intron	N/A	ENSP00000502349.1

Frequencies

GnomAD3 genomes AF: 0.00000698 AC: 1 AN: 143264 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000157

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000698 AC: 1 AN: 143264 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 70100

African (AFR) AF: 0.00 AC: 0 AN: 39656

American (AMR) AF: 0.00 AC: 0 AN: 14170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3204

East Asian (EAS) AF: 0.00 AC: 0 AN: 4922

South Asian (SAS) AF: 0.00 AC: 0 AN: 4546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.0000157 AC: 1 AN: 63528

Other (OTH) AF: 0.00 AC: 0 AN: 1972

Alfa AF: 0.00 Hom.: 70575

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.49
DANN	Benign	0.92
PhyloP100		-0.37

Splicing

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

Other links and lift over

dbSNP: rs2355230; hg19: chr1-239785165;