dbSNP rs3756618: LNPEP:c.*501T>A (chr5-97029034-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000395770.3(LNPEP):c.*501T>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 152,916 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.014 ( 52 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 0 hom. )

Consequence

LNPEP
ENST00000395770.3 splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.261

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 (SAS) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395770.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNPEP	NM_005575.3	MANE Select	c.*501T>A		3_prime_UTR	Exon 18 of 18	NP_005566.2
	LNPEP	NM_175920.4		c.*501T>A		3_prime_UTR	Exon 18 of 18	NP_787116.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LNPEP	ENST00000395770.3	TSL:1	c.*501T>A	splice_region	Exon 18 of 18	ENSP00000379117.3
LNPEP	ENST00000231368.10	TSL:1 MANE Select	c.*501T>A	3_prime_UTR	Exon 18 of 18	ENSP00000231368.5
LNPEP	ENST00000395770.3	TSL:1	c.*501T>A	3_prime_UTR	Exon 18 of 18	ENSP00000379117.3

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2180

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00595

Gnomad ASJ

AF:

0.0389

Gnomad EAS

AF:

0.0641

Gnomad SAS

AF:

0.0875

Gnomad FIN

AF:

0.0309

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.0139

GnomAD4 exome

AF:

0.00847

AC:

AN:

590

Hom.:

Cov.:

AF XY:

0.00617

AC XY:

AN XY:

324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00685

AC:

AN:

146

South Asian (SAS)

AF:

0.300

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00267

AC:

AN:

374

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

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:

0.0143

AC:

2182

AN:

152326

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1250

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41576

American (AMR)

AF:

0.00595

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0389

AC:

135

AN:

3472

East Asian (EAS)

AF:

0.0640

AC:

332

AN:

5186

South Asian (SAS)

AF:

0.0878

AC:

423

AN:

4820

European-Finnish (FIN)

AF:

0.0309

AC:

328

AN:

10622

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0115

AC:

783

AN:

68030

Other (OTH)

AF:

0.0142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

106

212

318

424

530

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:

0.0167

Hom.:

Bravo

AF:

0.00964

Asia WGS

AF:

0.0700

AC:

241

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

2.1

(source)

DANN

Benign

0.49

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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