chr15-89794962-A-G

Position:

• chr15-89794962-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001150.3(ANPEP):​c.2158-1836T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,538 control chromosomes in the GnomAD database, including 16,784 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 0.43 (16784 hom., cov: 31)
• Consequence: ANPEP NM_001150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANPEP	NM_001150.3	c.2158-1836T>C		intron_variant		ENST00000300060.7	NP_001141.2
ANPEP	NM_001381923.1	c.2158-1836T>C		intron_variant			NP_001368852.1
ANPEP	NM_001381924.1	c.2158-1836T>C		intron_variant			NP_001368853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANPEP	ENST00000300060.7	c.2158-1836T>C		intron_variant		1	NM_001150.3	ENSP00000300060	P1
ANPEP	ENST00000559874.2	c.2158-1836T>C		intron_variant		3		ENSP00000452934	P1
ANPEP	ENST00000560137.2	c.2158-1836T>C		intron_variant		3		ENSP00000453413	P1
ANPEP	ENST00000679248.1	c.2158-1836T>C		intron_variant				ENSP00000502886	P1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64461 AN: 151420 Hom.: 16754 Cov.: 31

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.426 AC: 64547 AN: 151538 Hom.: 16784 Cov.: 31 AF XY: 0.415 AC XY: 30699 AN XY: 74018

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.386

Alfa AF: 0.341 Hom.: 4479

Bravo AF: 0.446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs1439120; hg19: chr15-90338193;