rs8035491

Variant names:

• chr15-89799122-G-A
• rs8035491
• NM_001150.3:c.2009+138C>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.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 NM_001150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANPEP	NM_001150.3	MANE Select	c.2009+138C>T		intron	N/A	NP_001141.2	P15144
	ANPEP	NM_001381923.1		c.2009+138C>T		intron	N/A	NP_001368852.1	P15144
	ANPEP	NM_001381924.1		c.2009+138C>T		intron	N/A	NP_001368853.1	P15144

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANPEP	ENST00000300060.7	TSL:1 MANE Select	c.2009+138C>T		intron	N/A	ENSP00000300060.6	P15144
	ANPEP	ENST00000559874.2	TSL:3	c.2009+138C>T		intron	N/A	ENSP00000452934.2	P15144
	ANPEP	ENST00000560137.2	TSL:3	c.2009+138C>T		intron	N/A	ENSP00000453413.2	P15144

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

African (AFR) AF: 0.520 AC: 10436 AN: 20086

American (AMR) AF: 0.282 AC: 9065 AN: 32180

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 5615 AN: 18558

East Asian (EAS) AF: 0.190 AC: 6447 AN: 33932

South Asian (SAS) AF: 0.355 AC: 21972 AN: 61816

European-Finnish (FIN) AF: 0.407 AC: 16521 AN: 40564

Middle Eastern (MID) AF: 0.348 AC: 1070 AN: 3072

European-Non Finnish (NFE) AF: 0.475 AC: 253186 AN: 533166

Other (OTH) AF: 0.423 AC: 15901 AN: 37632

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

African (AFR) AF: 0.536 AC: 22208 AN: 41420

American (AMR) AF: 0.342 AC: 5218 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1021 AN: 3466

East Asian (EAS) AF: 0.209 AC: 1081 AN: 5166

South Asian (SAS) AF: 0.351 AC: 1689 AN: 4810

European-Finnish (FIN) AF: 0.399 AC: 4220 AN: 10578

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31852 AN: 67952

Other (OTH) AF: 0.415 AC: 877 AN: 2112

Alfa AF: 0.463 Hom.: 22932

Bravo AF: 0.451

Asia WGS AF: 0.295 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.71
PhyloP100		1.3
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: rs8035491; hg19: chr15-90342353; COSMIC: COSV55590946; COSMIC: COSV55590946;