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GeneBe

chr6:160585140-T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005577.4(LPA):c.4195A>C(p.Thr1399Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,538 control chromosomes in the GnomAD database, including 14,785 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.099 ( 949 hom., cov: 32)
Exomes 𝑓: 0.13 ( 13836 hom. )

Consequence

LPA
NM_005577.4 missense

Scores

3
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0027101636).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LPANM_005577.4 linkuse as main transcriptc.4195A>C p.Thr1399Pro missense_variant 26/39 ENST00000316300.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LPAENST00000316300.10 linkuse as main transcriptc.4195A>C p.Thr1399Pro missense_variant 26/391 NM_005577.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0990
AC:
15048
AN:
152070
Hom.:
949
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0267
Gnomad AMI
AF:
0.0340
Gnomad AMR
AF:
0.103
Gnomad ASJ
AF:
0.133
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.0898
Gnomad FIN
AF:
0.126
Gnomad MID
AF:
0.0506
Gnomad NFE
AF:
0.146
Gnomad OTH
AF:
0.0809
GnomAD3 exomes
AF:
0.110
AC:
27534
AN:
250654
Hom.:
1883
AF XY:
0.113
AC XY:
15278
AN XY:
135758
show subpopulations
Gnomad AFR exome
AF:
0.0223
Gnomad AMR exome
AF:
0.0959
Gnomad ASJ exome
AF:
0.131
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.100
Gnomad FIN exome
AF:
0.126
Gnomad NFE exome
AF:
0.141
Gnomad OTH exome
AF:
0.121
GnomAD4 exome
AF:
0.132
AC:
192617
AN:
1461350
Hom.:
13836
Cov.:
33
AF XY:
0.131
AC XY:
95584
AN XY:
727010
show subpopulations
Gnomad4 AFR exome
AF:
0.0223
Gnomad4 AMR exome
AF:
0.0968
Gnomad4 ASJ exome
AF:
0.133
Gnomad4 EAS exome
AF:
0.000378
Gnomad4 SAS exome
AF:
0.104
Gnomad4 FIN exome
AF:
0.128
Gnomad4 NFE exome
AF:
0.145
Gnomad4 OTH exome
AF:
0.118
GnomAD4 genome
AF:
0.0989
AC:
15053
AN:
152188
Hom.:
949
Cov.:
32
AF XY:
0.0976
AC XY:
7265
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.0266
Gnomad4 AMR
AF:
0.103
Gnomad4 ASJ
AF:
0.133
Gnomad4 EAS
AF:
0.00135
Gnomad4 SAS
AF:
0.0909
Gnomad4 FIN
AF:
0.126
Gnomad4 NFE
AF:
0.146
Gnomad4 OTH
AF:
0.0801
Alfa
AF:
0.125
Hom.:
1881
Bravo
AF:
0.0931
TwinsUK
AF:
0.139
AC:
515
ALSPAC
AF:
0.153
AC:
591
ESP6500AA
AF:
0.0278
AC:
122
ESP6500EA
AF:
0.149
AC:
1281
ExAC
AF:
0.109
AC:
13205
Asia WGS
AF:
0.0450
AC:
157
AN:
3476
EpiCase
AF:
0.144
EpiControl
AF:
0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.38
Cadd
Benign
22
Dann
Benign
0.92
Eigen
Benign
0.064
Eigen_PC
Benign
-0.18
FATHMM_MKL
Benign
0.43
N
MetaRNN
Benign
0.0027
T
MetaSVM
Benign
-0.64
T
MutationTaster
Benign
1.0
P;P
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-2.9
D
REVEL
Benign
0.26
Sift
Benign
0.036
D
Sift4G
Uncertain
0.025
D
Vest4
0.15
ClinPred
0.042
T
GERP RS
2.4
gMVP
0.65

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: rs41272110; hg19: chr6-161006172; COSMIC: COSV60315923; COSMIC: COSV60315923; API