Menu
GeneBe

6-160541153-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005577.4(LPA):c.5548T>C(p.Leu1850=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,614,070 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0029 ( 8 hom. )

Consequence

LPA
NM_005577.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.46
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-160541153-A-G is Benign according to our data. Variant chr6-160541153-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2657111.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.46 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LPANM_005577.4 linkuse as main transcriptc.5548T>C p.Leu1850= synonymous_variant 35/39 ENST00000316300.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LPAENST00000316300.10 linkuse as main transcriptc.5548T>C p.Leu1850= synonymous_variant 35/391 NM_005577.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00202
AC:
308
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00439
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.00245
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00345
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00235
AC:
591
AN:
251324
Hom.:
1
AF XY:
0.00241
AC XY:
328
AN XY:
135864
show subpopulations
Gnomad AFR exome
AF:
0.000556
Gnomad AMR exome
AF:
0.000983
Gnomad ASJ exome
AF:
0.00129
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00154
Gnomad FIN exome
AF:
0.00245
Gnomad NFE exome
AF:
0.00370
Gnomad OTH exome
AF:
0.00228
GnomAD4 exome
AF:
0.00291
AC:
4248
AN:
1461742
Hom.:
8
Cov.:
30
AF XY:
0.00285
AC XY:
2076
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.000329
Gnomad4 AMR exome
AF:
0.00112
Gnomad4 ASJ exome
AF:
0.00142
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00191
Gnomad4 FIN exome
AF:
0.00307
Gnomad4 NFE exome
AF:
0.00325
Gnomad4 OTH exome
AF:
0.00275
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00202
AC:
308
AN:
152328
Hom.:
0
Cov.:
32
AF XY:
0.00179
AC XY:
133
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.000433
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00245
Gnomad4 NFE
AF:
0.00345
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00264
Hom.:
0
Bravo
AF:
0.00180
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00376
EpiControl
AF:
0.00439

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023LPA: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
1.4
DANN
Benign
0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200086599; hg19: chr6-160962185; API