Genetic Variant LNPEP:c.*217C>T (chr5-97028750-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005575.3(LNPEP):c.*217C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LNPEP
NM_005575.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

Publications

23 publications found

Variant links:

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]

LNPEP links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LNPEP	NM_005575.3 link	c.*217C>T	3_prime_UTR_variant	Exon 18 of 18	ENST00000231368.10	NP_005566.2	Q9UIQ6-1
LNPEP	NM_175920.4 link	c.*217C>T	3_prime_UTR_variant	Exon 18 of 18		NP_787116.2	Q9UIQ6-2
LNPEP	XM_047417177.1 link	c.*217C>T	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 link	c.*217C>T		3_prime_UTR_variant	Exon 18 of 18	1	NM_005575.3	ENSP00000231368.5		Q9UIQ6-1
LNPEP	ENST00000395770.3 link	c.*217C>T		3_prime_UTR_variant	Exon 18 of 18	1		ENSP00000379117.3		Q9UIQ6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

250934

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

132076

African (AFR)

AF:

0.00

AC:

AN:

6922

American (AMR)

AF:

0.00

AC:

AN:

8486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7836

East Asian (EAS)

AF:

0.00

AC:

AN:

15204

South Asian (SAS)

AF:

0.00

AC:

AN:

25180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14704

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1146

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

156478

Other (OTH)

AF:

0.00

AC:

AN:

14978

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.55

PhyloP100

1.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over