15-34018399-C-T

Position:

• chr15-34018399-C-T

Variant summary

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

The ENST00000557872.1(CHRM5):​c.-142C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,980 control chromosomes in the GnomAD database, including 2,088 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 0.15 (2088 hom., cov: 32)
  • Exomes 𝑓: 0.060 (0 hom.)
• Consequence: CHRM5 ENST00000557872.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-407-28141C>T		intron_variant		ENST00000383263.7	NP_036257.1
AVEN	NM_020371.3	c.268-15190G>A		intron_variant		ENST00000306730.8	NP_065104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.-407-28141C>T		intron_variant		2	NM_012125.4	ENSP00000372750.5
AVEN	ENST00000306730.8	c.268-15190G>A		intron_variant		1	NM_020371.3	ENSP00000306822.3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22575 AN: 151778 Hom.: 2090 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.0917

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.0595 AC: 5 AN: 84 Hom.: 0 Cov.: 0 AF XY: 0.0536 AC XY: 3 AN XY: 56

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0588

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.149 AC: 22567 AN: 151896 Hom.: 2088 Cov.: 32 AF XY: 0.149 AC XY: 11047 AN XY: 74252

Gnomad4 AFR AF: 0.0697

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.00368

Gnomad4 SAS AF: 0.0916

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.162

Alfa AF: 0.0797 Hom.: 94

Bravo AF: 0.141

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.8
DANN	Benign	0.72

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: rs7162140; hg19: chr15-34310600;