chr1-239621865-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375978.1(CHRM3):​c.-312-10359C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 143,304 control chromosomes in the GnomAD database, including 36,767 homozygotes. 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 0.73 (36767 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.-312-10359C>A		intron_variant	Intron 3 of 6	ENST00000676153.1	NP_001362907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM3	ENST00000676153.1	c.-312-10359C>A		intron_variant	Intron 3 of 6		NM_001375978.1	ENSP00000502667.1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 104472 AN: 143192 Hom.: 36726 Cov.: 28

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.575

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.730 AC: 104557 AN: 143304 Hom.: 36767 Cov.: 28 AF XY: 0.732 AC XY: 51368 AN XY: 70192

African (AFR) AF: 0.879 AC: 34984 AN: 39778

American (AMR) AF: 0.658 AC: 9325 AN: 14164

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 1962 AN: 3202

East Asian (EAS) AF: 0.797 AC: 3913 AN: 4910

South Asian (SAS) AF: 0.647 AC: 2933 AN: 4530

European-Finnish (FIN) AF: 0.734 AC: 7464 AN: 10168

Middle Eastern (MID) AF: 0.564 AC: 141 AN: 250

European-Non Finnish (NFE) AF: 0.661 AC: 41956 AN: 63488

Other (OTH) AF: 0.693 AC: 1381 AN: 1992

Alfa AF: 0.674 Hom.: 70575

Bravo AF: 0.748

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.55
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;