15-34066989-T-C

Variant names:

• chr15-34066989-T-C
• rs613479
• NM_012125.4:c.*2673T>C

Variant summary

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

The NM_012125.4(CHRM5):​c.*2673T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,996 control chromosomes in the GnomAD database, including 20,535 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 (20527 hom., cov: 31)
  • Exomes 𝑓: 0.68 (8 hom.)
• Consequence: CHRM5 NM_012125.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836

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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.*2673T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000383263.7	NP_036257.1
CHRM5	NM_001320917.2	c.*2673T>C		3_prime_UTR_variant	Exon 2 of 2		NP_001307846.1
AVEN	XM_011521818.3	c.72+3599A>G		intron_variant	Intron 2 of 6		XP_011520120.1
AVEN	XM_047432882.1	c.72+3599A>G		intron_variant	Intron 3 of 7		XP_047288838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.*2673T>C		3_prime_UTR_variant	Exon 3 of 3	2	NM_012125.4	ENSP00000372750.5
AVEN	ENST00000675287.1	n.785-178A>G		intron_variant	Intron 2 of 11

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71860 AN: 151850 Hom.: 20520 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.679 AC: 19 AN: 28 Hom.: 8 Cov.: 0 AF XY: 0.792 AC XY: 19 AN XY: 24

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.473 AC: 71873 AN: 151968 Hom.: 20527 Cov.: 31 AF XY: 0.471 AC XY: 34953 AN XY: 74258

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.513

Alfa AF: 0.577 Hom.: 15774

Bravo AF: 0.455

Asia WGS AF: 0.509 AC: 1768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.5
DANN	Benign	0.75

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: rs613479; hg19: chr15-34359190;