chr1-239913308-A-G

Position:

• chr1-239913308-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375978.1(CHRM3):​c.*4084A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 166,896 control chromosomes in the GnomAD database, including 10,703 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 0.32 (10133 hom., cov: 32)
  • Exomes 𝑓: 0.27 (570 hom.)
• Consequence: CHRM3 NM_001375978.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM3	NM_001375978.1	c.*4084A>G		3_prime_UTR_variant	7/7	ENST00000676153.1	NP_001362907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM3	ENST00000676153.1	c.*4084A>G		3_prime_UTR_variant	7/7		NM_001375978.1	ENSP00000502667	P1
CHRM3	ENST00000255380.8	c.*4084A>G		3_prime_UTR_variant	5/5	1		ENSP00000255380	P1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48653 AN: 151888 Hom.: 10097 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.273 AC: 4068 AN: 14890 Hom.: 570 Cov.: 0 AF XY: 0.276 AC XY: 1952 AN XY: 7068

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.321 AC: 48739 AN: 152006 Hom.: 10133 Cov.: 32 AF XY: 0.318 AC XY: 23648 AN XY: 74314

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.259

Alfa AF: 0.232 Hom.: 9926

Bravo AF: 0.331

Asia WGS AF: 0.202 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.63
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs10495449; hg19: chr1-240076608;