dbSNP rs7755463: LPA:c.3630-137G>A (chr6-160591238-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.3630-137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,105,236 control chromosomes in the GnomAD database, including 4,015 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 0.10 ( 2537 hom., cov: 33)

Exomes 𝑓: 0.012 ( 1478 hom. )

Consequence

LPA
NM_005577.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.462

Publications

4 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4 link	c.3630-137G>A		intron_variant	Intron 22 of 38	ENST00000316300.10	NP_005568.2	P08519

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPA	ENST00000316300.10 link	c.3630-137G>A		intron_variant	Intron 22 of 38	1	NM_005577.4	ENSP00000321334.6		P08519

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15469

AN:

152096

Hom.:

2518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0381

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.0865

GnomAD4 exome

AF:

0.0119

AC:

11327

AN:

953024

Hom.:

1478

AF XY:

0.0103

AC XY:

4999

AN XY:

484894

show subpopulations

African (AFR)

AF:

0.346

AC:

7841

AN:

22692

American (AMR)

AF:

0.0226

AC:

764

AN:

33826

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

451

AN:

21492

East Asian (EAS)

AF:

0.00

AC:

AN:

33594

South Asian (SAS)

AF:

0.000973

AC:

AN:

67812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38260

Middle Eastern (MID)

AF:

0.0428

AC:

134

AN:

3130

European-Non Finnish (NFE)

AF:

0.00118

AC:

811

AN:

689274

Other (OTH)

AF:

0.0293

AC:

1260

AN:

42944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

445

891

1336

1782

2227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

384

576

768

960

<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:

0.102

AC:

15528

AN:

152212

Hom.:

2537

Cov.:

AF XY:

0.0984

AC XY:

7322

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.351

AC:

14545

AN:

41482

American (AMR)

AF:

0.0379

AC:

580

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00125

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00184

AC:

125

AN:

68026

Other (OTH)

AF:

0.0851

AC:

180

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

529

1057

1586

2114

2643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.0599

Hom.:

310

Bravo

AF:

0.116

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.0

(source)

DANN

Benign

0.53

PhyloP100

0.46

Mutation Taster

=100/0

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