Genetic Variant LNPEP:c.*614C>T (chr5-97029147-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005575.3(LNPEP):c.*614C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 152,316 control chromosomes in the GnomAD database, including 53 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 0.014 ( 53 hom., cov: 32)

Exomes 𝑓: 0.014 ( 0 hom. )

Consequence

LNPEP
NM_005575.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.510

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
LNPEP	NM_005575.3 link	c.*614C>T	3_prime_UTR_variant	Exon 18 of 18	ENST00000231368.10	NP_005566.2
LNPEP	NM_175920.4 link	c.*614C>T	3_prime_UTR_variant	Exon 18 of 18		NP_787116.2
LNPEP	XM_047417177.1 link	c.*614C>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.*614C>T		3_prime_UTR_variant	Exon 18 of 18	1	NM_005575.3	ENSP00000231368.5
LNPEP	ENST00000395770.3 link	c.*614C>T		downstream_gene_variant		1		ENSP00000379117.3

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2182

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00596

Gnomad ASJ

AF:

0.0389

Gnomad EAS

AF:

0.0643

Gnomad SAS

AF:

0.0877

Gnomad FIN

AF:

0.0310

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.0139

GnomAD4 exome

AF:

0.0143

AC:

AN:

140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00725

AC:

AN:

138

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0144

AC:

2184

AN:

152176

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1253

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41524

American (AMR)

AF:

0.00595

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0389

AC:

135

AN:

3468

East Asian (EAS)

AF:

0.0643

AC:

333

AN:

5182

South Asian (SAS)

AF:

0.0880

AC:

424

AN:

4818

European-Finnish (FIN)

AF:

0.0310

AC:

328

AN:

10576

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0115

AC:

783

AN:

68002

Other (OTH)

AF:

0.0142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

104

209

313

418

522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0145

Hom.:

Bravo

AF:

0.00964

Asia WGS

AF:

0.0700

AC:

241

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.5

(source)

DANN

Benign

0.60

PhyloP100

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over