dbSNP rs79818663: 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LNPEP	NM_005575.3 link	c.*594G>T	3_prime_UTR_variant	Exon 18 of 18	ENST00000231368.10	NP_005566.2	Q9UIQ6-1
LNPEP	NM_175920.4 link	c.*594G>T	3_prime_UTR_variant	Exon 18 of 18		NP_787116.2	Q9UIQ6-2
LNPEP	XM_047417177.1 link	c.*594G>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.*594G>T		3_prime_UTR_variant	Exon 18 of 18	1	NM_005575.3	ENSP00000231368.5		Q9UIQ6-1
LNPEP	ENST00000395770.3 link	c.*594G>T		downstream_gene_variant		1		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 v4.3

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

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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