rs6496603

Variant names:

• chr15-89785961-A-G
• rs6496603
• NM_001150.3:c.2752-460T>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.2752-460T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,054 control chromosomes in the GnomAD database, including 12,342 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 0.39 (12342 hom., cov: 33)
• Consequence: ANPEP NM_001150.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANPEP	NM_001150.3	c.2752-460T>C		intron_variant	Intron 20 of 20	ENST00000300060.7	NP_001141.2
ANPEP	NM_001381923.1	c.2752-460T>C		intron_variant	Intron 20 of 20		NP_001368852.1
ANPEP	NM_001381924.1	c.2752-460T>C		intron_variant	Intron 19 of 19		NP_001368853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANPEP	ENST00000300060.7	c.2752-460T>C		intron_variant	Intron 20 of 20	1	NM_001150.3	ENSP00000300060.6
ANPEP	ENST00000559874.2	c.2752-460T>C		intron_variant	Intron 20 of 20	3		ENSP00000452934.2
ANPEP	ENST00000560137.2	c.2752-460T>C		intron_variant	Intron 20 of 20	3		ENSP00000453413.2
ANPEP	ENST00000679248.1	c.2752-460T>C		intron_variant	Intron 21 of 21			ENSP00000502886.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59910 AN: 151936 Hom.: 12332 Cov.: 33

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.394 AC: 59969 AN: 152054 Hom.: 12342 Cov.: 33 AF XY: 0.385 AC XY: 28589 AN XY: 74330

African (AFR) AF: 0.496 AC: 20554 AN: 41456

American (AMR) AF: 0.332 AC: 5075 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1234 AN: 3468

East Asian (EAS) AF: 0.237 AC: 1230 AN: 5182

South Asian (SAS) AF: 0.418 AC: 2018 AN: 4826

European-Finnish (FIN) AF: 0.230 AC: 2427 AN: 10570

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25860 AN: 67972

Other (OTH) AF: 0.395 AC: 833 AN: 2110

Alfa AF: 0.383 Hom.: 6220

Bravo AF: 0.404

Asia WGS AF: 0.327 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.1
DANN	Benign	0.70
PhyloP100		0.74
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: rs6496603; hg19: chr15-90329192;