rs8035491

Positions:

• chr15-89799122-G-A

Variant summary

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

The ENST00000300060.7(ANPEP):​c.2009+138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 932,986 control chromosomes in the GnomAD database, including 93,085 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 0.45 (16149 hom., cov: 31)
  • Exomes 𝑓: 0.44 (76936 hom.)
• Consequence: ANPEP ENST00000300060.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANPEP	NM_001150.3	c.2009+138C>T		intron_variant		ENST00000300060.7	NP_001141.2
ANPEP	NM_001381923.1	c.2009+138C>T		intron_variant			NP_001368852.1
ANPEP	NM_001381924.1	c.2009+138C>T		intron_variant			NP_001368853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANPEP	ENST00000300060.7	c.2009+138C>T		intron_variant		1	NM_001150.3	ENSP00000300060	P1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68648 AN: 151862 Hom.: 16133 Cov.: 31

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.436 AC: 340213 AN: 781006 Hom.: 76936 AF XY: 0.432 AC XY: 173787 AN XY: 402260

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.452 AC: 68702 AN: 151980 Hom.: 16149 Cov.: 31 AF XY: 0.445 AC XY: 33072 AN XY: 74282

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.415

Alfa AF: 0.460 Hom.: 3381

Bravo AF: 0.451

Asia WGS AF: 0.295 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.71

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: rs8035491; hg19: chr15-90342353; COSMIC: COSV55590946; COSMIC: COSV55590946;