15-34022102-C-T

Position:

• chr15-34022102-C-T

Variant summary

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

The ENST00000306730.8(AVEN):​c.267+16678G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,124 control chromosomes in the GnomAD database, including 34,901 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 0.63 (34901 hom., cov: 32)
• Consequence: AVEN ENST00000306730.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-407-24438C>T		intron_variant		ENST00000383263.7	NP_036257.1
AVEN	NM_020371.3	c.267+16678G>A		intron_variant		ENST00000306730.8	NP_065104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AVEN	ENST00000306730.8	c.267+16678G>A		intron_variant		1	NM_020371.3	ENSP00000306822	P1
CHRM5	ENST00000383263.7	c.-407-24438C>T		intron_variant		2	NM_012125.4	ENSP00000372750	P1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95332 AN: 152006 Hom.: 34906 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.627 AC: 95345 AN: 152124 Hom.: 34901 Cov.: 32 AF XY: 0.625 AC XY: 46450 AN XY: 74350

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.696

Alfa AF: 0.763 Hom.: 20712

Bravo AF: 0.605

Asia WGS AF: 0.570 AC: 1981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.42

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: rs2702285; hg19: chr15-34314303;