rs517078

Positions:

• chr15-33985076-G-A
• chr15-33985076-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CHRM5	NM_012125.4	c.-408+15926G>A		intron_variant		ENST00000383263.7
AVEN	NM_020371.3	c.445+17956C>T		intron_variant		ENST00000306730.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVEN	ENST00000306730.8	c.445+17956C>T		intron_variant		1	NM_020371.3	P1
CHRM5	ENST00000383263.7	c.-408+15926G>A		intron_variant		2	NM_012125.4	P1
CHRM5	ENST00000560035.1	c.-76+15926G>A		intron_variant		4
AVEN	ENST00000675287.1	n.1815+17956C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.532

Alfa AF: 0.415 Hom.: 1391

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs517078; hg19: chr15-34277277;