NM_001150.3:c.2157+272C>G

Variant names:

• chr15-89797303-G-C
• rs753362
• NM_001150.3:c.2157+272C>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.2157+272C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 351,108 control chromosomes in the GnomAD database, including 82,183 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 0.69 (37435 hom., cov: 34)
  • Exomes 𝑓: 0.66 (44748 hom.)
• Consequence: ANPEP NM_001150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANPEP	NM_001150.3	c.2157+272C>G		intron_variant	Intron 15 of 20	ENST00000300060.7	NP_001141.2
ANPEP	NM_001381923.1	c.2157+272C>G		intron_variant	Intron 15 of 20		NP_001368852.1
ANPEP	NM_001381924.1	c.2157+272C>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.2157+272C>G		intron_variant	Intron 15 of 20	1	NM_001150.3	ENSP00000300060.6

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105481 AN: 152016 Hom.: 37404 Cov.: 34

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.701

GnomAD4 exome AF: 0.660 AC: 131275 AN: 198974 Hom.: 44748 AF XY: 0.661 AC XY: 66807 AN XY: 101094

African (AFR) AF: 0.807 AC: 4618 AN: 5722

American (AMR) AF: 0.542 AC: 3002 AN: 5536

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 5235 AN: 7362

East Asian (EAS) AF: 0.359 AC: 5540 AN: 15442

South Asian (SAS) AF: 0.661 AC: 6104 AN: 9238

European-Finnish (FIN) AF: 0.544 AC: 7595 AN: 13972

Middle Eastern (MID) AF: 0.770 AC: 755 AN: 980

European-Non Finnish (NFE) AF: 0.702 AC: 89605 AN: 127674

Other (OTH) AF: 0.676 AC: 8821 AN: 13048

GnomAD4 genome AF: 0.694 AC: 105555 AN: 152134 Hom.: 37435 Cov.: 34 AF XY: 0.681 AC XY: 50634 AN XY: 74380

African (AFR) AF: 0.808 AC: 33529 AN: 41518

American (AMR) AF: 0.592 AC: 9040 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2409 AN: 3470

East Asian (EAS) AF: 0.387 AC: 1996 AN: 5158

South Asian (SAS) AF: 0.629 AC: 3038 AN: 4828

European-Finnish (FIN) AF: 0.532 AC: 5622 AN: 10566

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47535 AN: 67994

Other (OTH) AF: 0.693 AC: 1463 AN: 2112

Alfa AF: 0.616 Hom.: 1963

Bravo AF: 0.702

Asia WGS AF: 0.508 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.42
PhyloP100		0.29
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: rs753362; hg19: chr15-90340534;