rs17239917

chr15-89790620-G-A

Variant summary

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

The NM_001150.3(ANPEP):c.2670-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,290,230 control chromosomes in the GnomAD database, including 19,164 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 0.14 (1669 hom., cov: 32)
  • Exomes 𝑓: 0.17 (17495 hom.)
• Consequence: ANPEP NM_001150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANPEP	NM_001150.3	c.2670-79C>T		intron_variant		ENST00000300060.7
ANPEP	NM_001381923.1	c.2670-79C>T		intron_variant
ANPEP	NM_001381924.1	c.2670-79C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANPEP	ENST00000300060.7	c.2670-79C>T		intron_variant		1	NM_001150.3	P1
ANPEP	ENST00000559874.2	c.2670-79C>T		intron_variant		3		P1
ANPEP	ENST00000560137.2	c.2670-79C>T		intron_variant		3		P1
ANPEP	ENST00000679248.1	c.2670-79C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21356 AN: 152074 Hom.: 1670 Cov.: 32

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.168 AC: 190943 AN: 1138038 Hom.: 17495 AF XY: 0.169 AC XY: 97896 AN XY: 577844

Gnomad4 AFR exome AF: 0.0992

Gnomad4 AMR exome AF: 0.0826

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.000719

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.140 AC: 21354 AN: 152192 Hom.: 1669 Cov.: 32 AF XY: 0.138 AC XY: 10271 AN XY: 74402

Gnomad4 AFR AF: 0.0962

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.162

Alfa AF: 0.174 Hom.: 4880

Bravo AF: 0.135

Asia WGS AF: 0.0730 AC: 254 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	0.89
Dann	Benign	0.75

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: rs17239917; hg19: chr15-90333851;