15-33976135-G-A

Position:

• chr15-33976135-G-A

Variant summary

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

The NM_012125.4(CHRM5):​c.-408+6985G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,066 control chromosomes in the GnomAD database, including 52,933 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 0.78 (52933 hom., cov: 31)
• Consequence: CHRM5 NM_012125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.668

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]

AVEN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.-408+6985G>A		intron_variant		ENST00000383263.7	NP_036257.1
AVEN	NM_020371.3	c.445+26897C>T		intron_variant		ENST00000306730.8	NP_065104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.-408+6985G>A		intron_variant		2	NM_012125.4	ENSP00000372750.5
AVEN	ENST00000306730.8	c.445+26897C>T		intron_variant		1	NM_020371.3	ENSP00000306822.3
CHRM5	ENST00000560035.1	c.-76+6985G>A		intron_variant		4		ENSP00000452742.1
AVEN	ENST00000675287.1	n.1815+26897C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117872 AN: 151948 Hom.: 52931 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.775 AC: 117892 AN: 152066 Hom.: 52933 Cov.: 31 AF XY: 0.783 AC XY: 58218 AN XY: 74360

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.895

Gnomad4 ASJ AF: 0.991

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.976

Gnomad4 OTH AF: 0.835

Alfa AF: 0.887 Hom.: 10547

Bravo AF: 0.745

Asia WGS AF: 0.881 AC: 3061 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.43

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: rs638169; hg19: chr15-34268336;