15-89793142-T-C

Variant names:

• chr15-89793142-T-C
• rs16943605
• NM_001150.3:c.2158-16A>G

Variant summary

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

The NM_001150.3(ANPEP):​c.2158-16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,605,492 control chromosomes in the GnomAD database, including 84,117 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 0.35 (9696 hom., cov: 31)
  • Exomes 𝑓: 0.32 (74421 hom.)
• Consequence: ANPEP NM_001150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANPEP	NM_001150.3	c.2158-16A>G		intron_variant	Intron 15 of 20	ENST00000300060.7	NP_001141.2
ANPEP	NM_001381923.1	c.2158-16A>G		intron_variant	Intron 15 of 20		NP_001368852.1
ANPEP	NM_001381924.1	c.2158-16A>G		intron_variant	Intron 14 of 19		NP_001368853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANPEP	ENST00000300060.7	c.2158-16A>G		intron_variant	Intron 15 of 20	1	NM_001150.3	ENSP00000300060.6

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52457 AN: 151778 Hom.: 9674 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.324

GnomAD2 exomes AF: 0.300 AC: 75352 AN: 250930 AF XY: 0.302

Gnomad AFR exome AF: 0.468

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.241

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.318

Gnomad OTH exome AF: 0.295

GnomAD4 exome AF: 0.316 AC: 459812 AN: 1453596 Hom.: 74421 Cov.: 29 AF XY: 0.317 AC XY: 229056 AN XY: 723626

African (AFR) AF: 0.475 AC: 15814 AN: 33284

American (AMR) AF: 0.243 AC: 10858 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6652 AN: 26048

East Asian (EAS) AF: 0.229 AC: 9073 AN: 39624

South Asian (SAS) AF: 0.330 AC: 28446 AN: 86074

European-Finnish (FIN) AF: 0.216 AC: 11516 AN: 53328

Middle Eastern (MID) AF: 0.287 AC: 1650 AN: 5748

European-Non Finnish (NFE) AF: 0.323 AC: 356896 AN: 1104668

Other (OTH) AF: 0.314 AC: 18907 AN: 60148

GnomAD4 genome AF: 0.346 AC: 52534 AN: 151896 Hom.: 9696 Cov.: 31 AF XY: 0.336 AC XY: 24961 AN XY: 74230

African (AFR) AF: 0.472 AC: 19543 AN: 41384

American (AMR) AF: 0.278 AC: 4243 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 886 AN: 3468

East Asian (EAS) AF: 0.236 AC: 1212 AN: 5146

South Asian (SAS) AF: 0.342 AC: 1642 AN: 4804

European-Finnish (FIN) AF: 0.195 AC: 2060 AN: 10556

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21630 AN: 67956

Other (OTH) AF: 0.325 AC: 686 AN: 2110

Alfa AF: 0.322 Hom.: 9821

Bravo AF: 0.356

Asia WGS AF: 0.303 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		-0.39
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: rs16943605; hg19: chr15-90336373; COSMIC: COSV55596115; COSMIC: COSV55596115;