chr15-34057604-T-C

Variant names:

• chr15-34057604-T-C
• rs554303
• NM_012125.4:c.-75-5039T>C

Variant summary

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

The NM_012125.4(CHRM5):​c.-75-5039T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,952 control chromosomes in the GnomAD database, including 32,296 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 0.63 (32296 hom., cov: 31)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 3 publications found

Genes affected

CHRM5 (HGNC:1954): (cholinergic receptor muscarinic 5) 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 clinical implications of this receptor are unknown; however, stimulation of this receptor is known to increase cyclic AMP levels. [provided by RefSeq, Jul 2008]

AVEN (HGNC:13509): (apoptosis and caspase activation inhibitor) Involved in negative regulation of apoptotic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012125.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM5	NM_012125.4	MANE Select	c.-75-5039T>C		intron	N/A	NP_036257.1	P08912
	CHRM5	NM_001320917.2		c.-75-5039T>C		intron	N/A	NP_001307846.1	P08912

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM5	ENST00000383263.7	TSL:2 MANE Select	c.-75-5039T>C		intron	N/A	ENSP00000372750.5	P08912
	CHRM5	ENST00000557872.1	TSL:1	c.-75-5039T>C		intron	N/A	ENSP00000453745.1	P08912
	CHRM5	ENST00000560035.1	TSL:4	c.-75-5039T>C		intron	N/A	ENSP00000452742.1	H0YKC0

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96297 AN: 151832 Hom.: 32291 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.634 AC: 96336 AN: 151952 Hom.: 32296 Cov.: 31 AF XY: 0.632 AC XY: 46955 AN XY: 74262

African (AFR) AF: 0.407 AC: 16851 AN: 41408

American (AMR) AF: 0.648 AC: 9901 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1943 AN: 3468

East Asian (EAS) AF: 0.651 AC: 3359 AN: 5156

South Asian (SAS) AF: 0.776 AC: 3740 AN: 4822

European-Finnish (FIN) AF: 0.675 AC: 7116 AN: 10548

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51143 AN: 67966

Other (OTH) AF: 0.657 AC: 1383 AN: 2106

Alfa AF: 0.703 Hom.: 16854

Bravo AF: 0.618

Asia WGS AF: 0.721 AC: 2509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.9
DANN	Benign	0.91
PhyloP100		0.0040
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: rs554303; hg19: chr15-34349805;