Variant rs3798220 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005577.4(LPA):c.5673A>G(p.Ile1891Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,614,110 control chromosomes in the GnomAD database, including 2,565 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.032 ( 306 hom., cov: 32)

Exomes 𝑓: 0.027 ( 2259 hom. )

Consequence

LPA
NM_005577.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.210

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:

LOC124901454 (HGNC:):

LOC124901454 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004463792).

BP6

Variant 6-160540105-T-C is Benign according to our data. Variant chr6-160540105-T-C is described in ClinVar as [Benign]. Clinvar id is 975030.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPA	NM_005577.4 linkuse as main transcript	c.5673A>G	p.Ile1891Met	missense_variant	36/39	ENST00000316300.10	NP_005568.2
LOC124901454	XR_007059844.1 linkuse as main transcript	n.1072T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10 linkuse as main transcript	c.5673A>G	p.Ile1891Met	missense_variant	36/39	1	NM_005577.4	ENSP00000321334	P1

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4885

AN:

152100

Hom.:

296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0931

Gnomad SAS

AF:

0.00478

Gnomad FIN

AF:

0.00933

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0445

GnomAD3 exomes

AF:

0.0557

AC:

14019

AN:

251472

Hom.:

1639

AF XY:

0.0455

AC XY:

6190

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00787

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.0896

Gnomad SAS exome

AF:

0.00392

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.0174

Gnomad OTH exome

AF:

0.0443

GnomAD4 exome

AF:

0.0268

AC:

39248

AN:

1461892

Hom.:

2259

Cov.:

AF XY:

0.0252

AC XY:

18337

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00594

Gnomad4 AMR exome

AF:

0.267

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.0954

Gnomad4 SAS exome

AF:

0.00443

Gnomad4 FIN exome

AF:

0.0109

Gnomad4 NFE exome

AF:

0.0187

Gnomad4 OTH exome

AF:

0.0250

GnomAD4 genome

AF:

0.0322

AC:

4908

AN:

152218

Hom.:

306

Cov.:

AF XY:

0.0336

AC XY:

2499

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00861

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0935

Gnomad4 SAS

AF:

0.00478

Gnomad4 FIN

AF:

0.00933

Gnomad4 NFE

AF:

0.0175

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0205

Hom.:

Bravo

AF:

0.0470

TwinsUK

AF:

0.0167

AC:

ALSPAC

AF:

0.0239

AC:

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.0195

AC:

168

ExAC

AF:

0.0448

AC:

5444

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

EpiCase

AF:

0.0168

EpiControl

AF:

0.0172

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LIPOPROTEIN(a) POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Aug 07, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.053

MetaRNN

Benign

0.0045

MetaSVM

Uncertain

-0.052

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.78

REVEL

Uncertain

0.32

Sift

Benign

0.12

Sift4G

Uncertain

0.022

Vest4

0.10

ClinPred

0.017

GERP RS

3.0

gMVP

0.26

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over