Genetic Variant NM_005577.4:c.-49T>C (chr6-160664263-A-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.-49T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 1,575,796 control chromosomes in the GnomAD database, including 582,072 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 0.89 ( 59980 hom., cov: 32)

Exomes 𝑓: 0.86 ( 522092 hom. )

Consequence

LPA
NM_005577.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.399

Publications

22 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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4 link	c.-49T>C		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.-49T>C		5_prime_UTR_variant	Exon 1 of 39	1	NM_005577.4	ENSP00000321334.6		P08519

Frequencies

GnomAD3 genomes

AF:

0.885

AC:

134688

AN:

152112

Hom.:

59928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.968

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.898

Gnomad ASJ

AF:

0.858

Gnomad EAS

AF:

0.806

Gnomad SAS

AF:

0.780

Gnomad FIN

AF:

0.849

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.857

Gnomad OTH

AF:

0.877

GnomAD2 exomes

AF:

0.764

AC:

112222

AN:

146928

AF XY:

0.753

show subpopulations

Gnomad AFR exome

AF:

0.937

Gnomad AMR exome

AF:

0.855

Gnomad ASJ exome

AF:

0.802

Gnomad EAS exome

AF:

0.675

Gnomad FIN exome

AF:

0.742

Gnomad NFE exome

AF:

0.753

Gnomad OTH exome

AF:

0.785

GnomAD4 exome

AF:

0.855

AC:

1217433

AN:

1423566

Hom.:

522092

Cov.:

AF XY:

0.852

AC XY:

604580

AN XY:

709458

show subpopulations

African (AFR)

AF:

0.970

AC:

31132

AN:

32094

American (AMR)

AF:

0.926

AC:

39360

AN:

42494

Ashkenazi Jewish (ASJ)

AF:

0.869

AC:

22428

AN:

25804

East Asian (EAS)

AF:

0.786

AC:

30986

AN:

39414

South Asian (SAS)

AF:

0.773

AC:

64423

AN:

83388

European-Finnish (FIN)

AF:

0.853

AC:

41860

AN:

49046

Middle Eastern (MID)

AF:

0.827

AC:

3348

AN:

4046

European-Non Finnish (NFE)

AF:

0.858

AC:

933438

AN:

1088270

Other (OTH)

AF:

0.855

AC:

50458

AN:

59010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

6772

13544

20317

27089

33861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20624

41248

61872

82496

103120

<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:

0.885

AC:

134795

AN:

152230

Hom.:

59980

Cov.:

AF XY:

0.882

AC XY:

65604

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.967

AC:

40191

AN:

41542

American (AMR)

AF:

0.898

AC:

13735

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.858

AC:

2979

AN:

3472

East Asian (EAS)

AF:

0.806

AC:

4175

AN:

5182

South Asian (SAS)

AF:

0.778

AC:

3749

AN:

4816

European-Finnish (FIN)

AF:

0.849

AC:

8988

AN:

10590

Middle Eastern (MID)

AF:

0.850

AC:

250

AN:

294

European-Non Finnish (NFE)

AF:

0.857

AC:

58292

AN:

68022

Other (OTH)

AF:

0.879

AC:

1859

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

761

1522

2283

3044

3805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.865

Hom.:

10534

Bravo

AF:

0.895

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

5.1

(source)

DANN

Benign

0.35

PhyloP100

0.40

PromoterAI

0.044

Neutral

(source)

Mutation Taster

=170/130

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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