15-34066124-T-C

Variant names:

• chr15-34066124-T-C
• rs541098
• NM_012125.4:c.*1808T>C

Variant summary

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

The NM_012125.4(CHRM5):​c.*1808T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,212 control chromosomes in the GnomAD database, including 46,325 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 (46318 hom., cov: 33)
  • Exomes 𝑓: 0.69 (7 hom.)
• Consequence: CHRM5 NM_012125.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM5	NM_012125.4	c.*1808T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000383263.7	NP_036257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM5	ENST00000383263.7	c.*1808T>C		3_prime_UTR_variant	Exon 3 of 3	2	NM_012125.4	ENSP00000372750.5
AVEN	ENST00000675287.1	n.974A>G		non_coding_transcript_exon_variant	Exon 4 of 12

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118295 AN: 152062 Hom.: 46290 Cov.: 33

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.767

GnomAD4 exome AF: 0.688 AC: 22 AN: 32 Hom.: 7 Cov.: 0 AF XY: 0.682 AC XY: 15 AN XY: 22

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.778 AC: 118380 AN: 152180 Hom.: 46318 Cov.: 33 AF XY: 0.779 AC XY: 57925 AN XY: 74380

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.962

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.769

Alfa AF: 0.784 Hom.: 58017

Bravo AF: 0.775

Asia WGS AF: 0.897 AC: 3120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
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: rs541098; hg19: chr15-34358325;