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rs3798220

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005577.4(LPA):c.5673A>G(p.Ile1891Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,614,110 control chromosomes in the GnomAD database, including 2,565 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.032 ( 306 hom., cov: 32)
Exomes 𝑓: 0.027 ( 2259 hom. )

Consequence

LPA
NM_005577.4 missense

Scores

3
11

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.210
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004463792).
BP6
Variant 6-160540105-T-C is Benign according to our data. Variant chr6-160540105-T-C is described in ClinVar as [Benign]. Clinvar id is 975030.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LPANM_005577.4 linkuse as main transcriptc.5673A>G p.Ile1891Met missense_variant 36/39 ENST00000316300.10
LOC124901454XR_007059844.1 linkuse as main transcriptn.1072T>C non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LPAENST00000316300.10 linkuse as main transcriptc.5673A>G p.Ile1891Met missense_variant 36/391 NM_005577.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0321
AC:
4885
AN:
152100
Hom.:
296
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00864
Gnomad AMI
AF:
0.0132
Gnomad AMR
AF:
0.172
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.0931
Gnomad SAS
AF:
0.00478
Gnomad FIN
AF:
0.00933
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0175
Gnomad OTH
AF:
0.0445
GnomAD3 exomes
AF:
0.0557
AC:
14019
AN:
251472
Hom.:
1639
AF XY:
0.0455
AC XY:
6190
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00787
Gnomad AMR exome
AF:
0.278
Gnomad ASJ exome
AF:
0.00218
Gnomad EAS exome
AF:
0.0896
Gnomad SAS exome
AF:
0.00392
Gnomad FIN exome
AF:
0.0104
Gnomad NFE exome
AF:
0.0174
Gnomad OTH exome
AF:
0.0443
GnomAD4 exome
AF:
0.0268
AC:
39248
AN:
1461892
Hom.:
2259
Cov.:
32
AF XY:
0.0252
AC XY:
18337
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00594
Gnomad4 AMR exome
AF:
0.267
Gnomad4 ASJ exome
AF:
0.00184
Gnomad4 EAS exome
AF:
0.0954
Gnomad4 SAS exome
AF:
0.00443
Gnomad4 FIN exome
AF:
0.0109
Gnomad4 NFE exome
AF:
0.0187
Gnomad4 OTH exome
AF:
0.0250
GnomAD4 genome
AF:
0.0322
AC:
4908
AN:
152218
Hom.:
306
Cov.:
32
AF XY:
0.0336
AC XY:
2499
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.00861
Gnomad4 AMR
AF:
0.173
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.0935
Gnomad4 SAS
AF:
0.00478
Gnomad4 FIN
AF:
0.00933
Gnomad4 NFE
AF:
0.0175
Gnomad4 OTH
AF:
0.0440
Alfa
AF:
0.0205
Hom.:
90
Bravo
AF:
0.0470
TwinsUK
AF:
0.0167
AC:
62
ALSPAC
AF:
0.0239
AC:
92
ESP6500AA
AF:
0.00862
AC:
38
ESP6500EA
AF:
0.0195
AC:
168
ExAC
AF:
0.0448
AC:
5444
Asia WGS
AF:
0.0340
AC:
119
AN:
3478
EpiCase
AF:
0.0168
EpiControl
AF:
0.0172

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

LIPOPROTEIN(a) POLYMORPHISM Benign:1
Benign, no assertion criteria providedliterature onlyOMIMAug 07, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.45
Cadd
Benign
12
Dann
Benign
0.97
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.053
N
MetaRNN
Benign
0.0045
T
MetaSVM
Uncertain
-0.052
T
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.78
N
REVEL
Uncertain
0.32
Sift
Benign
0.12
T
Sift4G
Uncertain
0.022
D
Vest4
0.10
ClinPred
0.017
T
GERP RS
3.0
gMVP
0.26

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

LitVar

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

Other links and lift over

dbSNP: rs3798220; hg19: chr6-160961137; COSMIC: COSV60302696; API