rs661968

Variant names:

• chr15-33968868-C-T
• rs661968
• NM_012125.4:c.-690C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012125.4(CHRM5):​c.-690C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,034 control chromosomes in the GnomAD database, including 54,276 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 0.80 (54276 hom., cov: 31)
  • Exomes 𝑓: 1.0 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRM5 NM_012125.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.967 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM5	NM_012125.4	MANE Select	c.-690C>T		5_prime_UTR	Exon 1 of 3	NP_036257.1	P08912
	AVEN	NM_020371.3	MANE Select	c.445+34164G>A		intron	N/A	NP_065104.1	Q9NQS1
	CHRM5	NM_001320917.2		c.-358C>T		5_prime_UTR	Exon 1 of 2	NP_001307846.1	P08912

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM5	ENST00000383263.7	TSL:2 MANE Select	c.-690C>T		5_prime_UTR	Exon 1 of 3	ENSP00000372750.5	P08912
	AVEN	ENST00000306730.8	TSL:1 MANE Select	c.445+34164G>A		intron	N/A	ENSP00000306822.3	Q9NQS1
	CHRM5	ENST00000560035.1	TSL:4	c.-358C>T		5_prime_UTR	Exon 1 of 2	ENSP00000452742.1	H0YKC0

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122293 AN: 151916 Hom.: 54275 Cov.: 31

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.992

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.841

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 1.00 AC: 10 AN: 10 Hom.: 5 Cov.: 0 AF XY: 1.00 AC XY: 6 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 10 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.805 AC: 122326 AN: 152034 Hom.: 54276 Cov.: 31 AF XY: 0.811 AC XY: 60276 AN XY: 74340

African (AFR) AF: 0.393 AC: 16271 AN: 41420

American (AMR) AF: 0.901 AC: 13751 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 3409 AN: 3472

East Asian (EAS) AF: 0.917 AC: 4750 AN: 5180

South Asian (SAS) AF: 0.944 AC: 4551 AN: 4820

European-Finnish (FIN) AF: 0.992 AC: 10524 AN: 10614

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66127 AN: 67948

Other (OTH) AF: 0.841 AC: 1777 AN: 2112

Alfa AF: 0.915 Hom.: 80691

Bravo AF: 0.778

Asia WGS AF: 0.886 AC: 3080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	14
DANN	Benign	0.91
PhyloP100		3.0
PromoterAI		-0.025	Neutral
Mutation Taster		=98/2	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: rs661968; hg19: chr15-34261069;