dbSNP rs10755578: LPA:c.4974-47G>C (chr6-160548706-C-G) – 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.4974-47G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,596,604 control chromosomes in the GnomAD database, including 174,330 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 0.42 ( 14018 hom., cov: 32)

Exomes 𝑓: 0.47 ( 160312 hom. )

Consequence

LPA
NM_005577.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.679

Publications

54 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005577.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPA	NM_005577.4	MANE Select	c.4974-47G>C		intron	N/A	NP_005568.2	P08519

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LPA	ENST00000316300.10	TSL:1 MANE Select	c.4974-47G>C	intron	N/A	ENSP00000321334.6	P08519
LPA	ENST00000870146.1		c.4971-47G>C	intron	N/A	ENSP00000540205.1
LPA	ENST00000870147.1		c.4656-47G>C	intron	N/A	ENSP00000540206.1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64409

AN:

151850

Hom.:

14020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.459

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.407

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.418

GnomAD2 exomes

AF:

0.439

AC:

109505

AN:

249318

AF XY:

0.445

show subpopulations

Gnomad AFR exome

AF:

0.340

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.449

Gnomad EAS exome

AF:

0.449

Gnomad FIN exome

AF:

0.483

Gnomad NFE exome

AF:

0.480

Gnomad OTH exome

AF:

0.442

GnomAD4 exome

AF:

0.469

AC:

677266

AN:

1444636

Hom.:

160312

Cov.:

AF XY:

0.469

AC XY:

337687

AN XY:

719774

show subpopulations

African (AFR)

AF:

0.342

AC:

11319

AN:

33050

American (AMR)

AF:

0.298

AC:

13312

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.452

AC:

11775

AN:

26042

East Asian (EAS)

AF:

0.458

AC:

18134

AN:

39554

South Asian (SAS)

AF:

0.471

AC:

40484

AN:

85880

European-Finnish (FIN)

AF:

0.481

AC:

25620

AN:

53300

Middle Eastern (MID)

AF:

0.459

AC:

2633

AN:

5732

European-Non Finnish (NFE)

AF:

0.480

AC:

526382

AN:

1096664

Other (OTH)

AF:

0.462

AC:

27607

AN:

59774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

18475

36951

55426

73902

92377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15406

30812

46218

61624

77030

<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:

0.424

AC:

64433

AN:

151968

Hom.:

14018

Cov.:

AF XY:

0.423

AC XY:

31443

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.336

AC:

13928

AN:

41458

American (AMR)

AF:

0.367

AC:

5604

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

1573

AN:

3462

East Asian (EAS)

AF:

0.451

AC:

2329

AN:

5162

South Asian (SAS)

AF:

0.457

AC:

2203

AN:

4816

European-Finnish (FIN)

AF:

0.481

AC:

5072

AN:

10546

Middle Eastern (MID)

AF:

0.407

AC:

118

AN:

290

European-Non Finnish (NFE)

AF:

0.474

AC:

32216

AN:

67954

Other (OTH)

AF:

0.420

AC:

886

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1871

3742

5613

7484

9355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<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:

0.453

Hom.:

2898

Bravo

AF:

0.407

Asia WGS

AF:

0.457

AC:

1591

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.30

PhyloP100

-0.68

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over