rs16943599

Variant names:

• chr15-89792795-C-A
• rs16943599
• NM_001150.3:c.2250-233G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-89792795-C-A
• chr15-89792795-C-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.2250-233G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,040 control chromosomes in the GnomAD database, including 9,101 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 0.34 (9101 hom., cov: 32)
• Consequence: ANPEP NM_001150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANPEP	NM_001150.3	c.2250-233G>T		intron_variant	Intron 16 of 20	ENST00000300060.7	NP_001141.2
ANPEP	NM_001381923.1	c.2250-233G>T		intron_variant	Intron 16 of 20		NP_001368852.1
ANPEP	NM_001381924.1	c.2250-233G>T		intron_variant	Intron 15 of 19		NP_001368853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANPEP	ENST00000300060.7	c.2250-233G>T		intron_variant	Intron 16 of 20	1	NM_001150.3	ENSP00000300060.6

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51117 AN: 151922 Hom.: 9091 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.337 AC: 51176 AN: 152040 Hom.: 9101 Cov.: 32 AF XY: 0.327 AC XY: 24303 AN XY: 74316

African (AFR) AF: 0.444 AC: 18394 AN: 41460

American (AMR) AF: 0.271 AC: 4136 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3472

East Asian (EAS) AF: 0.235 AC: 1210 AN: 5158

South Asian (SAS) AF: 0.341 AC: 1644 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2053 AN: 10596

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21566 AN: 67948

Other (OTH) AF: 0.317 AC: 669 AN: 2110

Alfa AF: 0.329 Hom.: 1121

Bravo AF: 0.346

Asia WGS AF: 0.295 AC: 1031 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	5.5
DANN	Benign	0.41
PhyloP100		-0.022
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16943599; hg19: chr15-90336026;