rs636842

Positions:

• chr15-33976415-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012125.4(CHRM5):​c.-408+7265T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,168 control chromosomes in the GnomAD database, including 7,359 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 0.28 (7359 hom., cov: 33)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM5	NM_012125.4	c.-408+7265T>G		intron_variant		ENST00000383263.7
AVEN	NM_020371.3	c.445+26617A>C		intron_variant		ENST00000306730.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVEN	ENST00000306730.8	c.445+26617A>C		intron_variant		1	NM_020371.3	P1
CHRM5	ENST00000383263.7	c.-408+7265T>G		intron_variant		2	NM_012125.4	P1
CHRM5	ENST00000560035.1	c.-76+7265T>G		intron_variant		4
AVEN	ENST00000675287.1	n.1815+26617A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41943 AN: 152052 Hom.: 7359 Cov.: 33

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.276 AC: 41947 AN: 152168 Hom.: 7359 Cov.: 33 AF XY: 0.269 AC XY: 20026 AN XY: 74396

Gnomad4 AFR AF: 0.0716

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.298

Alfa AF: 0.353 Hom.: 7609

Bravo AF: 0.271

Asia WGS AF: 0.189 AC: 655 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.8
DANN	Benign	0.70

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: rs636842; hg19: chr15-34268616;