dbSNP rs7765803: LPA:p.Leu1358Val (chr6-160586506-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005577.4(LPA):c.4072C>G(p.Leu1358Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,613,150 control chromosomes in the GnomAD database, including 103,992 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.41 ( 13236 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90756 hom. )

Consequence

LPA
NM_005577.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.09

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.1662784E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4 link	c.4072C>G	p.Leu1358Val	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.4072C>G	p.Leu1358Val	missense_variant	Exon 25 of 39	1	NM_005577.4	ENSP00000321334.6		P08519

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61511

AN:

151940

Hom.:

13206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.558

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.385

GnomAD3 exomes

AF:

0.353

AC:

88052

AN:

249370

Hom.:

16264

AF XY:

0.355

AC XY:

48028

AN XY:

135272

show subpopulations

Gnomad AFR exome

AF:

0.555

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.338

Gnomad EAS exome

AF:

0.396

Gnomad SAS exome

AF:

0.377

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.343

Gnomad OTH exome

AF:

0.343

GnomAD4 exome

AF:

0.348

AC:

508819

AN:

1461092

Hom.:

90756

Cov.:

AF XY:

0.349

AC XY:

253736

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.556

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.342

Gnomad4 EAS exome

AF:

0.429

Gnomad4 SAS exome

AF:

0.378

Gnomad4 FIN exome

AF:

0.370

Gnomad4 NFE exome

AF:

0.339

Gnomad4 OTH exome

AF:

0.361

GnomAD4 genome

AF:

0.405

AC:

61603

AN:

152058

Hom.:

13236

Cov.:

AF XY:

0.404

AC XY:

30048

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.558

Gnomad4 AMR

AF:

0.320

Gnomad4 ASJ

AF:

0.343

Gnomad4 EAS

AF:

0.400

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.370

Gnomad4 NFE

AF:

0.344

Gnomad4 OTH

AF:

0.391

Alfa

AF:

0.311

Hom.:

2348

Bravo

AF:

0.405

TwinsUK

AF:

0.329

AC:

1221

ALSPAC

AF:

0.335

AC:

1293

ESP6500AA

AF:

0.533

AC:

2242

ESP6500EA

AF:

0.344

AC:

2935

ExAC

AF:

0.360

AC:

43565

Asia WGS

AF:

0.405

AC:

1406

AN:

3476

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

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.0030

DANN

Benign

0.048

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00092

MetaRNN

Benign

0.000072

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

0.24

N;.

REVEL

Benign

0.047

Sift

Benign

1.0

T;.

Sift4G

Benign

0.85

T;T

Vest4

0.016

MPC

0.037

ClinPred

0.0015

GERP RS

-2.6

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over