Variant chr6-160585045-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005577.4(LPA):c.4289+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 1,613,234 control chromosomes in the GnomAD database, including 1,290 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 111 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1179 hom. )

Consequence

LPA
NM_005577.4 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: 3.51

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0551 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.4289+1G>A		splice_donor_variant, intron_variant		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.4289+1G>A		splice_donor_variant, intron_variant		1	NM_005577.4	ENSP00000321334.6		P08519

Frequencies

GnomAD3 genomes

AF:

0.0301

AC:

4571

AN:

152072

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00746

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0584

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0369

Gnomad FIN

AF:

0.0529

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0364

Gnomad OTH

AF:

0.0253

GnomAD3 exomes

AF:

0.0405

AC:

10118

AN:

249794

Hom.:

334

AF XY:

0.0388

AC XY:

5262

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.00709

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.0269

Gnomad EAS exome

AF:

0.000990

Gnomad SAS exome

AF:

0.0346

Gnomad FIN exome

AF:

0.0468

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0370

GnomAD4 exome

AF:

0.0367

AC:

53600

AN:

1461044

Hom.:

1179

Cov.:

AF XY:

0.0363

AC XY:

26406

AN XY:

726870

show subpopulations

Gnomad4 AFR exome

AF:

0.00583

Gnomad4 AMR exome

AF:

0.0978

Gnomad4 ASJ exome

AF:

0.0260

Gnomad4 EAS exome

AF:

0.000580

Gnomad4 SAS exome

AF:

0.0339

Gnomad4 FIN exome

AF:

0.0478

Gnomad4 NFE exome

AF:

0.0365

Gnomad4 OTH exome

AF:

0.0349

GnomAD4 genome

AF:

0.0300

AC:

4572

AN:

152190

Hom.:

111

Cov.:

AF XY:

0.0313

AC XY:

2331

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00744

Gnomad4 AMR

AF:

0.0582

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0371

Gnomad4 FIN

AF:

0.0529

Gnomad4 NFE

AF:

0.0365

Gnomad4 OTH

AF:

0.0250

Alfa

AF:

0.0321

Hom.:

157

Bravo

AF:

0.0304

TwinsUK

AF:

0.0332

AC:

123

ALSPAC

AF:

0.0371

AC:

143

ESP6500AA

AF:

0.00732

AC:

ESP6500EA

AF:

0.0346

AC:

295

ExAC

AF:

0.0369

AC:

4478

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0335

EpiControl

AF:

0.0344

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lipoprotein(a) deficiency, congenital

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 07, 2020

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Benign

0.93

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.75

GERP RS

2.6

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.77

SpliceAI score (max)

0.52

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.52

Position offset: 1

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