dbSNP rs661968: CHRM5:c.-690C>T (chr15-33968868-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.98

Publications

4 publications found

Variant links:

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]

CHRM5 links:

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 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM5	NM_012125.4 link	c.-690C>T		5_prime_UTR_variant	Exon 1 of 3	ENST00000383263.7	NP_036257.1
AVEN	NM_020371.3 link	c.445+34164G>A		intron_variant	Intron 2 of 5	ENST00000306730.8	NP_065104.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CHRM5	ENST00000383263.7 link	c.-690C>T	5_prime_UTR_variant	Exon 1 of 3	2	NM_012125.4	ENSP00000372750.5
AVEN	ENST00000306730.8 link	c.445+34164G>A	intron_variant	Intron 2 of 5	1	NM_020371.3	ENSP00000306822.3
CHRM5	ENST00000560035.1 link	c.-358C>T	5_prime_UTR_variant	Exon 1 of 2	4		ENSP00000452742.1
AVEN	ENST00000675287.1 link	n.1815+34164G>A	intron_variant	Intron 6 of 11

Frequencies

GnomAD3 genomes

AF:

0.805

AC:

122293

AN:

151916

Hom.:

54275

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.805

AC:

122326

AN:

152034

Hom.:

54276

Cov.:

AF XY:

0.811

AC XY:

60276

AN XY:

74340

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

698

1397

2095

2794

3492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

3.0

PromoterAI

-0.025

Neutral

(source)

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over