rs661968

Positions:

• chr15-33968868-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CHRM5	NM_012125.4	c.-690C>T		5_prime_UTR_variant	1/3	ENST00000383263.7
AVEN	NM_020371.3	c.445+34164G>A		intron_variant		ENST00000306730.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM5	ENST00000383263.7	c.-690C>T		5_prime_UTR_variant	1/3	2	NM_012125.4	P1
AVEN	ENST00000306730.8	c.445+34164G>A		intron_variant		1	NM_020371.3	P1
CHRM5	ENST00000560035.1	c.-358C>T		5_prime_UTR_variant	1/2	4
AVEN	ENST00000675287.1	n.1815+34164G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 NFE exome AF: 1.00

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

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.901

Gnomad4 ASJ AF: 0.982

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.992

Gnomad4 NFE AF: 0.973

Gnomad4 OTH AF: 0.841

Alfa AF: 0.940 Hom.: 63574

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	14
DANN	Benign	0.91

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

LitVar

Other links and lift over

dbSNP: rs661968; hg19: chr15-34261069;