rs499167

Positions:

• chr15-34056137-A-C

Variant summary

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

The NM_012125.4(CHRM5):​c.-75-6506A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 152,040 control chromosomes in the GnomAD database, including 33,462 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 0.65 (33462 hom., cov: 32)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-75-6506A>C		intron_variant		ENST00000383263.7	NP_036257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.-75-6506A>C		intron_variant		2	NM_012125.4	ENSP00000372750	P1
CHRM5	ENST00000557872.1	c.-75-6506A>C		intron_variant		1		ENSP00000453745	P1
CHRM5	ENST00000560035.1	c.-75-6506A>C		intron_variant		4		ENSP00000452742
AVEN	ENST00000675287.1	n.1637+6785T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98959 AN: 151922 Hom.: 33455 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.651 AC: 99006 AN: 152040 Hom.: 33462 Cov.: 32 AF XY: 0.649 AC XY: 48231 AN XY: 74324

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.776

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.665

Alfa AF: 0.712 Hom.: 9266

Bravo AF: 0.638

Asia WGS AF: 0.724 AC: 2520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.63

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: rs499167; hg19: chr15-34348338;