Genetic Variant LNPEP:c.*594G>T (chr5-97029127-G-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.*594G>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 0.0376 in 152,260 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.038 ( 185 hom., cov: 32)

Exomes 𝑓: 0.070 ( 0 hom. )

Consequence

LNPEP
NM_005575.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0170

Publications

5 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005575.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNPEP	NM_005575.3	MANE Select	c.*594G>T		3_prime_UTR	Exon 18 of 18	NP_005566.2	Q9UIQ6-1
	LNPEP	NM_175920.4		c.*594G>T		3_prime_UTR	Exon 18 of 18	NP_787116.2	Q9UIQ6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LNPEP	ENST00000231368.10	TSL:1 MANE Select	c.*594G>T	3_prime_UTR	Exon 18 of 18	ENSP00000231368.5	Q9UIQ6-1
LNPEP	ENST00000882743.1		c.*594G>T	3_prime_UTR	Exon 16 of 16	ENSP00000552802.1
LNPEP	ENST00000395770.3	TSL:1	c.*594G>T	downstream_gene	N/A	ENSP00000379117.3	Q9UIQ6-2

Frequencies

GnomAD3 genomes

AF:

0.0376

AC:

5715

AN:

152000

Hom.:

186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.0456

Gnomad ASJ

AF:

0.0705

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0551

Gnomad OTH

AF:

0.0574

GnomAD4 exome

AF:

0.0704

AC:

AN:

142

Hom.:

Cov.:

AF XY:

0.0769

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0725

AC:

AN:

138

South Asian (SAS)

AF:

0.00

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: 0.405

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:

0.0376

AC:

5713

AN:

152118

Hom.:

185

Cov.:

AF XY:

0.0358

AC XY:

2659

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0103

AC:

426

AN:

41488

American (AMR)

AF:

0.0455

AC:

696

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0705

AC:

244

AN:

3460

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.0289

AC:

139

AN:

4818

European-Finnish (FIN)

AF:

0.0186

AC:

197

AN:

10586

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0552

AC:

3749

AN:

67976

Other (OTH)

AF:

0.0573

AC:

121

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

273

545

818

1090

1363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0472

Hom.:

Bravo

AF:

0.0392

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.11

(source)

DANN

Benign

0.61

PhyloP100

-0.017

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over