Genetic Variant NM_005577.4:c.5156-127G>A (chr6-160548064-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.5156-127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 880,706 control chromosomes in the GnomAD database, including 418,605 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 0.98 ( 73034 hom., cov: 32)

Exomes 𝑓: 0.97 ( 345571 hom. )

Consequence

LPA
NM_005577.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.164

Publications

8 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPA	NM_005577.4 link	c.5156-127G>A		intron_variant	Intron 31 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.5156-127G>A		intron_variant	Intron 31 of 38	1	NM_005577.4	ENSP00000321334.6		P08519

Frequencies

GnomAD3 genomes

AF:

0.979

AC:

149026

AN:

152192

Hom.:

72972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.994

Gnomad AMI

AF:

0.989

Gnomad AMR

AF:

0.980

Gnomad ASJ

AF:

0.951

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.991

Gnomad FIN

AF:

0.982

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.969

Gnomad OTH

AF:

0.974

GnomAD4 exome

AF:

0.974

AC:

709443

AN:

728396

Hom.:

345571

AF XY:

0.975

AC XY:

376053

AN XY:

385844

show subpopulations

African (AFR)

AF:

0.994

AC:

17888

AN:

17988

American (AMR)

AF:

0.982

AC:

34816

AN:

35472

Ashkenazi Jewish (ASJ)

AF:

0.955

AC:

19078

AN:

19986

East Asian (EAS)

AF:

1.00

AC:

33582

AN:

33584

South Asian (SAS)

AF:

0.994

AC:

65178

AN:

65598

European-Finnish (FIN)

AF:

0.980

AC:

37642

AN:

38394

Middle Eastern (MID)

AF:

0.965

AC:

2902

AN:

3006

European-Non Finnish (NFE)

AF:

0.968

AC:

463340

AN:

478412

Other (OTH)

AF:

0.974

AC:

35017

AN:

35956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

969

1938

2908

3877

4846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5166

10332

15498

20664

25830

<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:

0.979

AC:

149147

AN:

152310

Hom.:

73034

Cov.:

AF XY:

0.980

AC XY:

72985

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.994

AC:

41334

AN:

41570

American (AMR)

AF:

0.980

AC:

14996

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.951

AC:

3303

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5168

AN:

5170

South Asian (SAS)

AF:

0.991

AC:

4778

AN:

4822

European-Finnish (FIN)

AF:

0.982

AC:

10428

AN:

10622

Middle Eastern (MID)

AF:

0.966

AC:

284

AN:

294

European-Non Finnish (NFE)

AF:

0.969

AC:

65897

AN:

68036

Other (OTH)

AF:

0.974

AC:

2057

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

162

324

486

648

810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.975

Hom.:

48813

Bravo

AF:

0.979

Asia WGS

AF:

0.995

AC:

3461

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.8

(source)

DANN

Benign

0.51

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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