15-34013530-T-C

Position:

• chr15-34013530-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012125.4(CHRM5):​c.-407-33010T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,152 control chromosomes in the GnomAD database, including 36,903 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 0.64 (36903 hom., cov: 33)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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]

AVEN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-407-33010T>C		intron_variant		ENST00000383263.7	NP_036257.1
AVEN	NM_020371.3	c.268-10321A>G		intron_variant		ENST00000306730.8	NP_065104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.-407-33010T>C		intron_variant		2	NM_012125.4	ENSP00000372750.5
AVEN	ENST00000306730.8	c.268-10321A>G		intron_variant		1	NM_020371.3	ENSP00000306822.3
CHRM5	ENST00000560035.1	c.-76+44380T>C		intron_variant		4		ENSP00000452742.1
AVEN	ENST00000675287.1	n.1638-10321A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97855 AN: 152034 Hom.: 36903 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.643 AC: 97878 AN: 152152 Hom.: 36903 Cov.: 33 AF XY: 0.642 AC XY: 47765 AN XY: 74372

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.709

Alfa AF: 0.751 Hom.: 18706

Bravo AF: 0.619

Asia WGS AF: 0.599 AC: 2080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.41

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: rs2684953; hg19: chr15-34305731;