rs2684941

Positions:

• chr15-34039581-G-A
• chr15-34039581-G-C

Variant summary

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

The NM_012125.4(CHRM5):​c.-407-6959G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,940 control chromosomes in the GnomAD database, including 21,033 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 0.49 (21033 hom., cov: 31)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

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 = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-407-6959G>A		intron_variant		ENST00000383263.7	NP_036257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.-407-6959G>A		intron_variant		2	NM_012125.4	ENSP00000372750	P1
CHRM5	ENST00000557872.1	c.-76+21116G>A		intron_variant		1		ENSP00000453745	P1
CHRM5	ENST00000560035.1	c.-75-23062G>A		intron_variant		4		ENSP00000452742
AVEN	ENST00000675287.1	n.1637+23341C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74443 AN: 151822 Hom.: 21027 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.490 AC: 74465 AN: 151940 Hom.: 21033 Cov.: 31 AF XY: 0.488 AC XY: 36234 AN XY: 74236

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.527

Alfa AF: 0.563 Hom.: 6908

Bravo AF: 0.473

Asia WGS AF: 0.535 AC: 1862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2684941; hg19: chr15-34331782;