1-239622120-A-G

Variant names:

• chr1-239622120-A-G
• rs2165870
• NM_001375978.1:c.-312-10104A>G

Variant summary

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

The NM_001375978.1(CHRM3):​c.-312-10104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,066 control chromosomes in the GnomAD database, including 43,341 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 0.74 (43341 hom., cov: 31)
• Consequence: CHRM3 NM_001375978.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 17 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.-312-10104A>G		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.-312-10104A>G		intron_variant	Intron 3 of 6		NM_001375978.1	ENSP00000502667.1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113107 AN: 151948 Hom.: 43302 Cov.: 31

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.744 AC: 113190 AN: 152066 Hom.: 43341 Cov.: 31 AF XY: 0.744 AC XY: 55319 AN XY: 74308

African (AFR) AF: 0.930 AC: 38633 AN: 41532

American (AMR) AF: 0.656 AC: 10015 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2117 AN: 3468

East Asian (EAS) AF: 0.813 AC: 4181 AN: 5140

South Asian (SAS) AF: 0.645 AC: 3099 AN: 4806

European-Finnish (FIN) AF: 0.734 AC: 7752 AN: 10564

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.665 AC: 45218 AN: 67962

Other (OTH) AF: 0.708 AC: 1497 AN: 2114

Alfa AF: 0.631 Hom.: 2099

Bravo AF: 0.748

Asia WGS AF: 0.691 AC: 2400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.59
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs2165870; hg19: chr1-239785420;