rs636842

Variant names:

• chr15-33976415-T-G
• rs636842
• NM_012125.4:c.-408+7265T>G

Variant summary

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

The NM_012125.4(CHRM5):​c.-408+7265T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,168 control chromosomes in the GnomAD database, including 7,359 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 0.28 (7359 hom., cov: 33)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 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.-408+7265T>G		intron	N/A	NP_036257.1	P08912
	AVEN	NM_020371.3	MANE Select	c.445+26617A>C		intron	N/A	NP_065104.1	Q9NQS1
	CHRM5	NM_001320917.2		c.-76+7265T>G		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.-408+7265T>G		intron	N/A	ENSP00000372750.5	P08912
	AVEN	ENST00000306730.8	TSL:1 MANE Select	c.445+26617A>C		intron	N/A	ENSP00000306822.3	Q9NQS1
	AVEN	ENST00000964283.1		c.445+26617A>C		intron	N/A	ENSP00000634342.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41943 AN: 152052 Hom.: 7359 Cov.: 33

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.276 AC: 41947 AN: 152168 Hom.: 7359 Cov.: 33 AF XY: 0.269 AC XY: 20026 AN XY: 74396

African (AFR) AF: 0.0716 AC: 2974 AN: 41556

American (AMR) AF: 0.362 AC: 5523 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1252 AN: 3468

East Asian (EAS) AF: 0.119 AC: 617 AN: 5188

South Asian (SAS) AF: 0.236 AC: 1136 AN: 4820

European-Finnish (FIN) AF: 0.297 AC: 3140 AN: 10580

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26294 AN: 67970

Other (OTH) AF: 0.298 AC: 628 AN: 2106

Alfa AF: 0.323 Hom.: 10212

Bravo AF: 0.271

Asia WGS AF: 0.189 AC: 655 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.8
DANN	Benign	0.70
PhyloP100		-0.62
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: rs636842; hg19: chr15-34268616;