15-89785320-G-C

Position:

• chr15-89785320-G-C

Variant summary

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

The NM_001150.3(ANPEP):​c.*29C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,612,628 control chromosomes in the GnomAD database, including 263,185 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 0.60 (29698 hom., cov: 32)
  • Exomes 𝑓: 0.56 (233487 hom.)
• Consequence: ANPEP NM_001150.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

Genes affected

ANPEP (HGNC:500): (alanyl aminopeptidase, membrane) Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Its function in proximal tubular epithelial cells and other cell types is less clear. The large extracellular carboxyterminal domain contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with known enzymes of this class showed that CD13 and aminopeptidase N are identical. The latter enzyme was thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the CNS. This membrane-bound zinc metalloprotease is known to serve as a receptor for the HCoV-229E alphacoronavirus as well as other non-human coronaviruses. This gene has also been shown to promote angiogenesis, tumor growth, and metastasis and defects in this gene are associated with various types of leukemia and lymphoma. [provided by RefSeq, Apr 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANPEP	NM_001150.3	c.*29C>G		3_prime_UTR_variant	21/21	ENST00000300060.7
ANPEP	NM_001381923.1	c.*29C>G		3_prime_UTR_variant	21/21
ANPEP	NM_001381924.1	c.*29C>G		3_prime_UTR_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANPEP	ENST00000300060.7	c.*29C>G		3_prime_UTR_variant	21/21	1	NM_001150.3	P1
ANPEP	ENST00000559874.2	c.*29C>G		3_prime_UTR_variant	21/21	3		P1
ANPEP	ENST00000560137.2	c.*29C>G		3_prime_UTR_variant	21/21	3		P1
ANPEP	ENST00000679248.1	c.*29C>G		3_prime_UTR_variant	22/22			P1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91696 AN: 151898 Hom.: 29661 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.597

GnomAD3 exomes AF: 0.521 AC: 130804 AN: 250912 Hom.: 36737 AF XY: 0.531 AC XY: 71997 AN XY: 135634

Gnomad AFR exome AF: 0.827

Gnomad AMR exome AF: 0.371

Gnomad ASJ exome AF: 0.580

Gnomad EAS exome AF: 0.243

Gnomad SAS exome AF: 0.622

Gnomad FIN exome AF: 0.374

Gnomad NFE exome AF: 0.563

Gnomad OTH exome AF: 0.533

GnomAD4 exome AF: 0.558 AC: 815078 AN: 1460612 Hom.: 233487 Cov.: 42 AF XY: 0.561 AC XY: 407629 AN XY: 726516

Gnomad4 AFR exome AF: 0.838

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.574

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.623

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.570

Gnomad4 OTH exome AF: 0.562

GnomAD4 genome AF: 0.604 AC: 91784 AN: 152016 Hom.: 29698 Cov.: 32 AF XY: 0.589 AC XY: 43779 AN XY: 74314

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.595

Alfa AF: 0.577 Hom.: 4612

Bravo AF: 0.617

Asia WGS AF: 0.431 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10584; hg19: chr15-90328551; COSMIC: COSV55590903;