15-34060377-G-T

Variant names:

• chr15-34060377-G-T
• rs623941
• NM_012125.4:c.-75-2266G>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.-75-2266G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 151,886 control chromosomes in the GnomAD database, including 30,095 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 0.62 (30095 hom., cov: 31)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012125.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM5	NM_012125.4	MANE Select	c.-75-2266G>T		intron	N/A	NP_036257.1
	CHRM5	NM_001320917.2		c.-75-2266G>T		intron	N/A	NP_001307846.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM5	ENST00000383263.7	TSL:2 MANE Select	c.-75-2266G>T		intron	N/A	ENSP00000372750.5
	CHRM5	ENST00000557872.1	TSL:1	c.-75-2266G>T		intron	N/A	ENSP00000453745.1
	CHRM5	ENST00000560035.1	TSL:4	c.-75-2266G>T		intron	N/A	ENSP00000452742.1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94109 AN: 151768 Hom.: 30064 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.620 AC: 94190 AN: 151886 Hom.: 30095 Cov.: 31 AF XY: 0.622 AC XY: 46149 AN XY: 74210

African (AFR) AF: 0.470 AC: 19441 AN: 41376

American (AMR) AF: 0.712 AC: 10869 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1854 AN: 3466

East Asian (EAS) AF: 0.806 AC: 4171 AN: 5172

South Asian (SAS) AF: 0.635 AC: 3055 AN: 4812

European-Finnish (FIN) AF: 0.634 AC: 6680 AN: 10528

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46090 AN: 67950

Other (OTH) AF: 0.631 AC: 1333 AN: 2112

Alfa AF: 0.658 Hom.: 86610

Bravo AF: 0.620

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.58
PhyloP100		-0.14
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: rs623941; hg19: chr15-34352578;