rs4779656

Positions:

• chr15-34032402-A-G

Variant summary

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

The NM_012125.4(CHRM5):​c.-407-14138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,170 control chromosomes in the GnomAD database, including 2,064 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 (2064 hom., cov: 32)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-407-14138A>G		intron_variant		ENST00000383263.7	NP_036257.1
AVEN	NM_020371.3	c.267+6378T>C		intron_variant		ENST00000306730.8	NP_065104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.-407-14138A>G		intron_variant		2	NM_012125.4	ENSP00000372750.5
AVEN	ENST00000306730.8	c.267+6378T>C		intron_variant		1	NM_020371.3	ENSP00000306822.3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22526 AN: 152052 Hom.: 2066 Cov.: 32

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.148 AC: 22518 AN: 152170 Hom.: 2064 Cov.: 32 AF XY: 0.148 AC XY: 11013 AN XY: 74390

Gnomad4 AFR AF: 0.0693

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.0913

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.164

Alfa AF: 0.173 Hom.: 1123

Bravo AF: 0.141

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.0
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4779656; hg19: chr15-34324603;