Genetic Variant LPA:c.-21G>A (chr6-160664235-C-T) – 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.-21G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,600,988 control chromosomes in the GnomAD database, including 42,473 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 7331 hom., cov: 32)

Exomes 𝑓: 0.20 ( 35142 hom. )

Consequence

LPA
NM_005577.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0590

Publications

29 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 (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4 link	c.-21G>A		5_prime_UTR_variant	Exon 1 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.-21G>A		5_prime_UTR_variant	Exon 1 of 39	1	NM_005577.4	ENSP00000321334.6		P08519

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42516

AN:

151938

Hom.:

7314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.449

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.366

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.460

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.260

GnomAD2 exomes

AF:

0.238

AC:

46840

AN:

196820

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.446

Gnomad AMR exome

AF:

0.474

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.422

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.200

AC:

289140

AN:

1448932

Hom.:

35142

Cov.:

AF XY:

0.199

AC XY:

143571

AN XY:

721106

show subpopulations

African (AFR)

AF:

0.446

AC:

14716

AN:

33002

American (AMR)

AF:

0.499

AC:

21974

AN:

43996

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

4165

AN:

26064

East Asian (EAS)

AF:

0.449

AC:

17789

AN:

39590

South Asian (SAS)

AF:

0.281

AC:

23850

AN:

85018

European-Finnish (FIN)

AF:

0.178

AC:

8940

AN:

50312

Middle Eastern (MID)

AF:

0.194

AC:

802

AN:

4126

European-Non Finnish (NFE)

AF:

0.166

AC:

183910

AN:

1106936

Other (OTH)

AF:

0.217

AC:

12994

AN:

59888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

10293

20585

30878

41170

51463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7016

14032

21048

28064

35080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.280

AC:

42575

AN:

152056

Hom.:

7331

Cov.:

AF XY:

0.283

AC XY:

21031

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.450

AC:

18639

AN:

41464

American (AMR)

AF:

0.366

AC:

5593

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

516

AN:

3470

East Asian (EAS)

AF:

0.460

AC:

2377

AN:

5168

South Asian (SAS)

AF:

0.313

AC:

1511

AN:

4822

European-Finnish (FIN)

AF:

0.177

AC:

1869

AN:

10548

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11388

AN:

67990

Other (OTH)

AF:

0.257

AC:

543

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1439

2878

4318

5757

7196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.143

Hom.:

366

Bravo

AF:

0.303

Asia WGS

AF:

0.386

AC:

1341

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

6.4

(source)

DANN

Benign

0.57

PhyloP100

-0.059

PromoterAI

0.0048

Neutral

(source)

Mutation Taster

=300/0

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

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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