Variant rs41265936 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005577.4(LPA):c.5465G>C(p.Gly1822Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,614,044 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.018 ( 87 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 94 hom. )

Consequence

LPA
NM_005577.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.10

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058689117).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0607 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.5465G>C	p.Gly1822Ala	missense_variant	34/39	ENST00000316300.10	NP_005568.2	P08519

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10 linkuse as main transcript	c.5465G>C	p.Gly1822Ala	missense_variant	34/39	1	NM_005577.4	ENSP00000321334.6		P08519

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2735

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0625

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00495

AC:

1244

AN:

251448

Hom.:

AF XY:

0.00377

AC XY:

513

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0640

Gnomad AMR exome

AF:

0.00387

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000237

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00198

AC:

2892

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1260

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0655

Gnomad4 AMR exome

AF:

0.00364

Gnomad4 ASJ exome

AF:

0.00214

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.00475

GnomAD4 genome

AF:

0.0181

AC:

2748

AN:

152214

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1323

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0627

Gnomad4 AMR

AF:

0.00654

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.000779

Hom.:

Bravo

AF:

0.0198

ESP6500AA

AF:

0.0635

AC:

280

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00619

AC:

751

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.11

Eigen

Benign

0.16

Eigen_PC

Benign

-0.067

FATHMM_MKL

Benign

0.48

MetaRNN

Benign

0.0059

MetaSVM

Uncertain

0.31

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.45

Sift

Benign

0.064

Sift4G

Uncertain

0.017

Vest4

0.39

MVP

0.54

ClinPred

0.079

GERP RS

2.5

gMVP

0.38

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