rs4779656

Variant names:

• chr15-34032402-A-G
• rs4779656
• NM_012125.4:c.-407-14138A>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.-407-14138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,170 control chromosomes in the GnomAD database, including 2,064 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 0.15 (2064 hom., cov: 32)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-407-14138A>G		intron_variant	Intron 1 of 2	ENST00000383263.7	NP_036257.1
AVEN	NM_020371.3	c.267+6378T>C		intron_variant	Intron 1 of 5	ENST00000306730.8	NP_065104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.-407-14138A>G		intron_variant	Intron 1 of 2	2	NM_012125.4	ENSP00000372750.5
AVEN	ENST00000306730.8	c.267+6378T>C		intron_variant	Intron 1 of 5	1	NM_020371.3	ENSP00000306822.3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22526 AN: 152052 Hom.: 2066 Cov.: 32

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.148 AC: 22518 AN: 152170 Hom.: 2064 Cov.: 32 AF XY: 0.148 AC XY: 11013 AN XY: 74390

African (AFR) AF: 0.0693 AC: 2878 AN: 41534

American (AMR) AF: 0.148 AC: 2266 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1196 AN: 3462

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5188

South Asian (SAS) AF: 0.0913 AC: 440 AN: 4820

European-Finnish (FIN) AF: 0.230 AC: 2429 AN: 10568

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12695 AN: 67996

Other (OTH) AF: 0.164 AC: 346 AN: 2110

Alfa AF: 0.174 Hom.: 1291

Bravo AF: 0.141

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.0
DANN	Benign	0.58
PhyloP100		-0.087
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4779656; hg19: chr15-34324603;