rs16943605

chr15-89793142-T-Cchr15-89793142-T-G

Variant summary

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

The NM_001150.3(ANPEP):c.2158-16A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,605,492 control chromosomes in the GnomAD database, including 84,117 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 0.35 (9696 hom., cov: 31)
  • Exomes 𝑓: 0.32 (74421 hom.)
• Consequence: ANPEP NM_001150.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386

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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANPEP	NM_001150.3	c.2158-16A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000300060.7
ANPEP	NM_001381923.1	c.2158-16A>G		splice_polypyrimidine_tract_variant, intron_variant
ANPEP	NM_001381924.1	c.2158-16A>G		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANPEP	ENST00000300060.7	c.2158-16A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001150.3	P1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52457 AN: 151778 Hom.: 9674 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.324

GnomAD3 exomes AF: 0.300 AC: 75352 AN: 250930 Hom.: 12022 AF XY: 0.302 AC XY: 40966 AN XY: 135652

Gnomad AFR exome AF: 0.468

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.241

Gnomad SAS exome AF: 0.334

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.318

Gnomad OTH exome AF: 0.295

GnomAD4 exome AF: 0.316 AC: 459812 AN: 1453596 Hom.: 74421 Cov.: 29 AF XY: 0.317 AC XY: 229056 AN XY: 723626

Gnomad4 AFR exome AF: 0.475

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.346 AC: 52534 AN: 151896 Hom.: 9696 Cov.: 31 AF XY: 0.336 AC XY: 24961 AN XY: 74230

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.325

Alfa AF: 0.317 Hom.: 7396

Bravo AF: 0.356

Asia WGS AF: 0.303 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	12
Dann	Benign	0.84

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: rs16943605; hg19: chr15-90336373; COSMIC: COSV55596115; COSMIC: COSV55596115;