rs10519901

Variant names:

• chr15-33987067-T-C
• rs10519901
• NM_012125.4:c.-408+17917T>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+17917T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0766 in 152,300 control chromosomes in the GnomAD database, including 586 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 0.077 (586 hom., cov: 34)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 1 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]

ENSG00000287840 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-408+17917T>C		intron_variant	Intron 1 of 2	ENST00000383263.7	NP_036257.1
AVEN	NM_020371.3	c.445+15965A>G		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+17917T>C		intron_variant	Intron 1 of 2	2	NM_012125.4	ENSP00000372750.5
AVEN	ENST00000306730.8	c.445+15965A>G		intron_variant	Intron 2 of 5	1	NM_020371.3	ENSP00000306822.3

Frequencies

GnomAD3 genomes AF: 0.0766 AC: 11660 AN: 152182 Hom.: 587 Cov.: 34

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.0713

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

GnomAD4 genome AF: 0.0766 AC: 11666 AN: 152300 Hom.: 586 Cov.: 34 AF XY: 0.0802 AC XY: 5972 AN XY: 74470

African (AFR) AF: 0.0472 AC: 1963 AN: 41572

American (AMR) AF: 0.0472 AC: 723 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3472

East Asian (EAS) AF: 0.186 AC: 961 AN: 5176

South Asian (SAS) AF: 0.212 AC: 1020 AN: 4820

European-Finnish (FIN) AF: 0.107 AC: 1137 AN: 10612

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0784 AC: 5333 AN: 68028

Other (OTH) AF: 0.0734 AC: 155 AN: 2112

Alfa AF: 0.0763 Hom.: 261

Bravo AF: 0.0687

Asia WGS AF: 0.200 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.53
DANN	Benign	0.79
PhyloP100		-1.1
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: rs10519901; hg19: chr15-34279268;