rs8030094

Variant names:

• chr15-34044681-G-A
• rs8030094
• NM_012125.4:c.-407-1859G>A

Variant summary

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

The NM_012125.4(CHRM5):​c.-407-1859G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,074 control chromosomes in the GnomAD database, including 2,222 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 0.16 (2222 hom., cov: 32)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 8 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=-0.91).
• 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 rank	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-407-1859G>A		intron_variant	Intron 1 of 2	ENST00000383263.7	NP_036257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.-407-1859G>A		intron_variant	Intron 1 of 2	2	NM_012125.4	ENSP00000372750.5
CHRM5	ENST00000557872.1	c.-75-17962G>A		intron_variant	Intron 1 of 1	1		ENSP00000453745.1
CHRM5	ENST00000560035.1	c.-75-17962G>A		intron_variant	Intron 1 of 1	4		ENSP00000452742.1
AVEN	ENST00000675287.1	n.1637+18241C>T		intron_variant	Intron 5 of 11

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24054 AN: 151956 Hom.: 2224 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.158 AC: 24054 AN: 152074 Hom.: 2222 Cov.: 32 AF XY: 0.158 AC XY: 11753 AN XY: 74344

African (AFR) AF: 0.106 AC: 4383 AN: 41420

American (AMR) AF: 0.151 AC: 2316 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3470

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5190

South Asian (SAS) AF: 0.0908 AC: 438 AN: 4824

European-Finnish (FIN) AF: 0.230 AC: 2431 AN: 10570

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12665 AN: 67996

Other (OTH) AF: 0.168 AC: 355 AN: 2114

Alfa AF: 0.171 Hom.: 894

Bravo AF: 0.152

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-0.16
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: rs8030094; hg19: chr15-34336882;