rs17239917

Variant names:

• chr15-89790620-G-A
• rs17239917
• NM_001150.3:c.2670-79C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001150.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANPEP	NM_001150.3	MANE Select	c.2670-79C>T		intron	N/A	NP_001141.2
	ANPEP	NM_001381923.1		c.2670-79C>T		intron	N/A	NP_001368852.1
	ANPEP	NM_001381924.1		c.2670-79C>T		intron	N/A	NP_001368853.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANPEP	ENST00000300060.7	TSL:1 MANE Select	c.2670-79C>T		intron	N/A	ENSP00000300060.6
	ANPEP	ENST00000559874.2	TSL:3	c.2670-79C>T		intron	N/A	ENSP00000452934.2
	ANPEP	ENST00000560137.2	TSL:3	c.2670-79C>T		intron	N/A	ENSP00000453413.2

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

African (AFR) AF: 0.0992 AC: 2670 AN: 26926

American (AMR) AF: 0.0826 AC: 3292 AN: 39870

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 4627 AN: 23676

East Asian (EAS) AF: 0.000719 AC: 27 AN: 37560

South Asian (SAS) AF: 0.177 AC: 13675 AN: 77100

European-Finnish (FIN) AF: 0.139 AC: 7072 AN: 51024

Middle Eastern (MID) AF: 0.231 AC: 1179 AN: 5110

European-Non Finnish (NFE) AF: 0.182 AC: 150221 AN: 827056

Other (OTH) AF: 0.165 AC: 8180 AN: 49716

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

African (AFR) AF: 0.0962 AC: 3993 AN: 41514

American (AMR) AF: 0.110 AC: 1679 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 671 AN: 3466

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5178

South Asian (SAS) AF: 0.161 AC: 774 AN: 4818

European-Finnish (FIN) AF: 0.138 AC: 1467 AN: 10612

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12350 AN: 67992

Other (OTH) AF: 0.162 AC: 341 AN: 2110

Alfa AF: 0.167 Hom.: 7582

Bravo AF: 0.135

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.89
DANN	Benign	0.75
PhyloP100		-0.35
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: rs17239917; hg19: chr15-90333851;