dbSNP rs7765781: LPA:p.Leu1372Val (chr6-160586464-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005577.4(LPA):c.4114C>G(p.Leu1372Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,611,430 control chromosomes in the GnomAD database, including 105,168 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 13897 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91271 hom. )

Consequence

LPA
NM_005577.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

Publications

40 publications found

Variant links:

Genes affected

LPA (HGNC:6667): (lipoprotein(a)) The protein encoded by this gene is a serine proteinase that inhibits the activity of tissue-type plasminogen activator I. The encoded protein constitutes a substantial portion of lipoprotein(a) and is proteolytically cleaved, resulting in fragments that attach to atherosclerotic lesions and promote thrombogenesis. Elevated plasma levels of this protein are linked to atherosclerosis. Depending on the individual, the encoded protein contains 2-43 copies of kringle-type domains. The allele represented here contains 15 copies of the kringle-type repeats and corresponds to that found in the reference genome sequence. [provided by RefSeq, Dec 2009]

LPA 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 (MetaRNN=1.6006301E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4 link	c.4114C>G	p.Leu1372Val	missense_variant	Exon 25 of 39	ENST00000316300.10	NP_005568.2	P08519

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10 link	c.4114C>G	p.Leu1372Val	missense_variant	Exon 25 of 39	1	NM_005577.4	ENSP00000321334.6		P08519

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62681

AN:

151960

Hom.:

13864

Cov.:

show subpopulations

Gnomad AFR

AF:

0.585

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.388

GnomAD2 exomes

AF:

0.355

AC:

88414

AN:

249128

AF XY:

0.356

show subpopulations

Gnomad AFR exome

AF:

0.583

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.338

Gnomad EAS exome

AF:

0.395

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.343

Gnomad OTH exome

AF:

0.343

GnomAD4 exome

AF:

0.349

AC:

508989

AN:

1459352

Hom.:

91271

Cov.:

AF XY:

0.350

AC XY:

253823

AN XY:

726116

show subpopulations

African (AFR)

AF:

0.584

AC:

19487

AN:

33378

American (AMR)

AF:

0.257

AC:

11475

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

8921

AN:

26104

East Asian (EAS)

AF:

0.428

AC:

16993

AN:

39662

South Asian (SAS)

AF:

0.378

AC:

32586

AN:

86206

European-Finnish (FIN)

AF:

0.370

AC:

19762

AN:

53388

Middle Eastern (MID)

AF:

0.399

AC:

2295

AN:

5756

European-Non Finnish (NFE)

AF:

0.338

AC:

375638

AN:

1109874

Other (OTH)

AF:

0.362

AC:

21832

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

17816

35631

53447

71262

89078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.413

AC:

62777

AN:

152078

Hom.:

13897

Cov.:

AF XY:

0.412

AC XY:

30618

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.585

AC:

24292

AN:

41490

American (AMR)

AF:

0.321

AC:

4904

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1191

AN:

3470

East Asian (EAS)

AF:

0.399

AC:

2060

AN:

5164

South Asian (SAS)

AF:

0.359

AC:

1728

AN:

4820

European-Finnish (FIN)

AF:

0.370

AC:

3914

AN:

10576

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.344

AC:

23402

AN:

67968

Other (OTH)

AF:

0.394

AC:

831

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1832

3664

5495

7327

9159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.359

Hom.:

7593

Bravo

AF:

0.414

TwinsUK

AF:

0.329

AC:

1221

ALSPAC

AF:

0.335

AC:

1293

ESP6500AA

AF:

0.560

AC:

2188

ESP6500EA

AF:

0.343

AC:

2865

ExAC

AF:

0.362

AC:

43787

Asia WGS

AF:

0.406

AC:

1409

AN:

3478

EpiCase

AF:

0.350

EpiControl

AF:

0.333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.0040

(source)

DANN

Benign

0.13

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00042

MetaRNN

Benign

0.000016

MetaSVM

Benign

-1.1

PhyloP100

-1.9

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.25

REVEL

Benign

0.078

Sift

Benign

0.97

Sift4G

Benign

0.82

Vest4

0.080

ClinPred

0.00080

GERP RS

-2.2

gMVP

0.13

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.

rs7765781

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