rs517078

Variant names:

• chr15-33985076-G-A
• rs517078
• NM_012125.4:c.-408+15926G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-33985076-G-A
• chr15-33985076-G-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.-408+15926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,934 control chromosomes in the GnomAD database, including 20,705 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 0.47 (20705 hom., cov: 31)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-408+15926G>A		intron_variant	Intron 1 of 2	ENST00000383263.7	NP_036257.1
AVEN	NM_020371.3	c.445+17956C>T		intron_variant	Intron 2 of 5	ENST00000306730.8	NP_065104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.-408+15926G>A		intron_variant	Intron 1 of 2	2	NM_012125.4	ENSP00000372750.5
AVEN	ENST00000306730.8	c.445+17956C>T		intron_variant	Intron 2 of 5	1	NM_020371.3	ENSP00000306822.3
CHRM5	ENST00000560035.1	c.-76+15926G>A		intron_variant	Intron 1 of 1	4		ENSP00000452742.1
AVEN	ENST00000675287.1	n.1815+17956C>T		intron_variant	Intron 6 of 11

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72146 AN: 151816 Hom.: 20697 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.475 AC: 72156 AN: 151934 Hom.: 20705 Cov.: 31 AF XY: 0.473 AC XY: 35139 AN XY: 74254

African (AFR) AF: 0.139 AC: 5772 AN: 41462

American (AMR) AF: 0.569 AC: 8687 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1623 AN: 3456

East Asian (EAS) AF: 0.523 AC: 2691 AN: 5142

South Asian (SAS) AF: 0.524 AC: 2490 AN: 4750

European-Finnish (FIN) AF: 0.540 AC: 5711 AN: 10582

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43424 AN: 67954

Other (OTH) AF: 0.532 AC: 1122 AN: 2110

Alfa AF: 0.400 Hom.: 1412

Bravo AF: 0.460

Asia WGS AF: 0.511 AC: 1774 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.43
PhyloP100		0.47
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: rs517078; hg19: chr15-34277277;