rs2339350

Variant names:

• chr15-34024775-A-C
• rs2339350
• NM_012125.4:c.-407-21765A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-34024775-A-C
• chr15-34024775-A-G
• chr15-34024775-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012125.4(CHRM5):​c.-407-21765A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 150,254 control chromosomes in the GnomAD database, including 73,960 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 0.99 (73960 hom., cov: 26)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-407-21765A>C		intron_variant	Intron 1 of 2	ENST00000383263.7	NP_036257.1
AVEN	NM_020371.3	c.267+14005T>G		intron_variant	Intron 1 of 5	ENST00000306730.8	NP_065104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.-407-21765A>C		intron_variant	Intron 1 of 2	2	NM_012125.4	ENSP00000372750.5
AVEN	ENST00000306730.8	c.267+14005T>G		intron_variant	Intron 1 of 5	1	NM_020371.3	ENSP00000306822.3

Frequencies

GnomAD3 genomes AF: 0.992 AC: 148965 AN: 150148 Hom.: 73907 Cov.: 26

Gnomad AFR AF: 0.973

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.993

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

GnomAD4 genome AF: 0.992 AC: 149071 AN: 150254 Hom.: 73960 Cov.: 26 AF XY: 0.992 AC XY: 72587 AN XY: 73166

African (AFR) AF: 0.973 AC: 39955 AN: 41074

American (AMR) AF: 0.998 AC: 15100 AN: 15134

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3464 AN: 3464

East Asian (EAS) AF: 1.00 AC: 5072 AN: 5074

South Asian (SAS) AF: 1.00 AC: 4768 AN: 4768

European-Finnish (FIN) AF: 1.00 AC: 9692 AN: 9694

Middle Eastern (MID) AF: 1.00 AC: 292 AN: 292

European-Non Finnish (NFE) AF: 1.00 AC: 67753 AN: 67764

Other (OTH) AF: 0.993 AC: 2065 AN: 2080

Alfa AF: 0.994 Hom.: 3674

Bravo AF: 0.991

Asia WGS AF: 0.997 AC: 3468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2339350; hg19: chr15-34316976;