chr1-239635621-C-T

Variant names:

• chr1-239635621-C-T
• rs6700643
• NM_001375978.1:c.-250+3335C>T

Variant summary

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

The NM_001375978.1(CHRM3):​c.-250+3335C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,052 control chromosomes in the GnomAD database, including 29,004 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 0.61 (29004 hom., cov: 33)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.-250+3335C>T		intron_variant	Intron 4 of 6	ENST00000676153.1	NP_001362907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM3	ENST00000676153.1	c.-250+3335C>T		intron_variant	Intron 4 of 6		NM_001375978.1	ENSP00000502667.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93235 AN: 151934 Hom.: 28977 Cov.: 33

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.614 AC: 93310 AN: 152052 Hom.: 29004 Cov.: 33 AF XY: 0.621 AC XY: 46166 AN XY: 74316

African (AFR) AF: 0.588 AC: 24375 AN: 41470

American (AMR) AF: 0.663 AC: 10119 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1793 AN: 3468

East Asian (EAS) AF: 0.833 AC: 4297 AN: 5158

South Asian (SAS) AF: 0.638 AC: 3075 AN: 4816

European-Finnish (FIN) AF: 0.680 AC: 7198 AN: 10578

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40553 AN: 67978

Other (OTH) AF: 0.590 AC: 1246 AN: 2112

Alfa AF: 0.612 Hom.: 3581

Bravo AF: 0.613

Asia WGS AF: 0.680 AC: 2363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6700643; hg19: chr1-239798921;