15-89807388-C-G

Variant names:

• chr15-89807388-C-G
• rs35408448
• NM_001150.3:c.-223-582G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001150.3(ANPEP):​c.-223-582G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 152,234 control chromosomes in the GnomAD database, including 462 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 0.071 (462 hom., cov: 33)
• Consequence: ANPEP NM_001150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANPEP	NM_001150.3	c.-223-582G>C		intron_variant	Intron 1 of 20	ENST00000300060.7	NP_001141.2
ANPEP	NM_001381923.1	c.-226-579G>C		intron_variant	Intron 1 of 20		NP_001368852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANPEP	ENST00000300060.7	c.-223-582G>C		intron_variant	Intron 1 of 20	1	NM_001150.3	ENSP00000300060.6
ANPEP	ENST00000559874.2	c.-223-582G>C		intron_variant	Intron 1 of 20	3		ENSP00000452934.2
ANPEP	ENST00000560137.2	c.-362-443G>C		intron_variant	Intron 1 of 20	3		ENSP00000453413.2
ANPEP	ENST00000679248.1	c.-223-582G>C		intron_variant	Intron 2 of 21			ENSP00000502886.1

Frequencies

GnomAD3 genomes AF: 0.0706 AC: 10740 AN: 152116 Hom.: 462 Cov.: 33

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.0875

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.0731

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0705 AC: 10736 AN: 152234 Hom.: 462 Cov.: 33 AF XY: 0.0694 AC XY: 5163 AN XY: 74428

African (AFR) AF: 0.0373 AC: 1548 AN: 41540

American (AMR) AF: 0.0492 AC: 753 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0655 AC: 227 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5180

South Asian (SAS) AF: 0.0696 AC: 336 AN: 4830

European-Finnish (FIN) AF: 0.0875 AC: 927 AN: 10596

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0994 AC: 6761 AN: 68004

Other (OTH) AF: 0.0719 AC: 152 AN: 2114

Alfa AF: 0.0379 Hom.: 28

Bravo AF: 0.0665

Asia WGS AF: 0.0330 AC: 116 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	0.51
DANN	Benign	0.44
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35408448; hg19: chr15-90350619;