chr5-97028750-C-G

Variant names:

• chr5-97028750-C-G
• rs39602
• NM_005575.3:c.*217C>G

Variant summary

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

The NM_005575.3(LNPEP):​c.*217C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 402,094 control chromosomes in the GnomAD database, including 70,472 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 0.59 (26502 hom., cov: 33)
  • Exomes 𝑓: 0.59 (43970 hom.)
• Consequence: LNPEP NM_005575.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 23 publications found

Genes affected

LNPEP (HGNC:6656): (leucyl and cystinyl aminopeptidase) This gene encodes a zinc-dependent aminopeptidase that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step in the conversion of angiotensinogen to angiotensin IV (AT4) and is also a receptor for AT4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNPEP	NM_005575.3	c.*217C>G		3_prime_UTR_variant	Exon 18 of 18	ENST00000231368.10	NP_005566.2
LNPEP	NM_175920.4	c.*217C>G		3_prime_UTR_variant	Exon 18 of 18		NP_787116.2
LNPEP	XM_047417177.1	c.*217C>G		3_prime_UTR_variant	Exon 16 of 16		XP_047273133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNPEP	ENST00000231368.10	c.*217C>G		3_prime_UTR_variant	Exon 18 of 18	1	NM_005575.3	ENSP00000231368.5
LNPEP	ENST00000395770.3	c.*217C>G		3_prime_UTR_variant	Exon 18 of 18	1		ENSP00000379117.3

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89659 AN: 151980 Hom.: 26497 Cov.: 33

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.591 AC: 147760 AN: 249994 Hom.: 43970 Cov.: 4 AF XY: 0.594 AC XY: 78193 AN XY: 131560

African (AFR) AF: 0.582 AC: 4006 AN: 6888

American (AMR) AF: 0.651 AC: 5507 AN: 8458

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 5414 AN: 7824

East Asian (EAS) AF: 0.603 AC: 9127 AN: 15132

South Asian (SAS) AF: 0.640 AC: 16064 AN: 25102

European-Finnish (FIN) AF: 0.597 AC: 8756 AN: 14660

Middle Eastern (MID) AF: 0.709 AC: 807 AN: 1138

European-Non Finnish (NFE) AF: 0.572 AC: 89163 AN: 155870

Other (OTH) AF: 0.598 AC: 8916 AN: 14922

GnomAD4 genome AF: 0.590 AC: 89696 AN: 152100 Hom.: 26502 Cov.: 33 AF XY: 0.593 AC XY: 44064 AN XY: 74350

African (AFR) AF: 0.581 AC: 24091 AN: 41482

American (AMR) AF: 0.635 AC: 9702 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2437 AN: 3472

East Asian (EAS) AF: 0.621 AC: 3213 AN: 5170

South Asian (SAS) AF: 0.628 AC: 3034 AN: 4830

European-Finnish (FIN) AF: 0.609 AC: 6436 AN: 10562

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38739 AN: 67982

Other (OTH) AF: 0.609 AC: 1288 AN: 2114

Alfa AF: 0.424 Hom.: 1055

Bravo AF: 0.598

Asia WGS AF: 0.549 AC: 1910 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		1.3
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: rs39602; hg19: chr5-96364454;