15-89802996-A-G

Variant names:

• chr15-89802996-A-G
• rs7168849
• NM_001150.3:c.1569+243T>C

Variant summary

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

The NM_001150.3(ANPEP):​c.1569+243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,038 control chromosomes in the GnomAD database, including 5,142 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 0.21 (5142 hom., cov: 32)
• Consequence: ANPEP NM_001150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANPEP	NM_001150.3	c.1569+243T>C		intron_variant	Intron 10 of 20	ENST00000300060.7	NP_001141.2
ANPEP	NM_001381923.1	c.1569+243T>C		intron_variant	Intron 10 of 20		NP_001368852.1
ANPEP	NM_001381924.1	c.1569+243T>C		intron_variant	Intron 9 of 19		NP_001368853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANPEP	ENST00000300060.7	c.1569+243T>C		intron_variant	Intron 10 of 20	1	NM_001150.3	ENSP00000300060.6

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31984 AN: 151920 Hom.: 5103 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.211 AC: 32094 AN: 152038 Hom.: 5142 Cov.: 32 AF XY: 0.214 AC XY: 15944 AN XY: 74338

African (AFR) AF: 0.418 AC: 17307 AN: 41434

American (AMR) AF: 0.314 AC: 4800 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3470

East Asian (EAS) AF: 0.262 AC: 1354 AN: 5162

South Asian (SAS) AF: 0.146 AC: 703 AN: 4822

European-Finnish (FIN) AF: 0.109 AC: 1152 AN: 10598

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0884 AC: 6010 AN: 67950

Other (OTH) AF: 0.212 AC: 447 AN: 2108

Alfa AF: 0.138 Hom.: 3454

Bravo AF: 0.242

Asia WGS AF: 0.250 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.71
PhyloP100		-0.33
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: rs7168849; hg19: chr15-90346227; COSMIC: COSV55595554; COSMIC: COSV55595554;