GeneBe

rs4941543

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002298.5(LCP1):​c.1597A>T​(p.Lys533*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LCP1
NM_002298.5 stop_gained

Scores

2
1
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.67

Publications

39 publications found
Variant links:
Genes affected
LCP1 (HGNC:6528): (lymphocyte cytosolic protein 1) Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. Plastin 1 (otherwise known as Fimbrin) is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). However, L-plastin has been found in many types of malignant human cells of non-hemopoietic origin suggesting that its expression is induced accompanying tumorigenesis in solid tissues. [provided by RefSeq, Jul 2008]
CPB2-AS1 (HGNC:39898): (CPB2 antisense RNA 1)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002298.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
LCP1
NM_002298.5
MANE Select
c.1597A>Tp.Lys533*
stop_gained
Exon 14 of 16NP_002289.2

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
LCP1
ENST00000323076.7
TSL:1 MANE Select
c.1597A>Tp.Lys533*
stop_gained
Exon 14 of 16ENSP00000315757.2
LCP1
ENST00000398576.6
TSL:5
c.1597A>Tp.Lys533*
stop_gained
Exon 17 of 19ENSP00000381581.1
LCP1
ENST00000674665.1
c.304A>Tp.Lys102*
stop_gained
Exon 3 of 5ENSP00000501964.1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1461486
Hom.:
0
Cov.:
40
AF XY:
0.00
AC XY:
0
AN XY:
727076
African (AFR)
AF:
0.00
AC:
0
AN:
33464
American (AMR)
AF:
0.00
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39660
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53336
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111780
Other (OTH)
AF:
0.00
AC:
0
AN:
60378
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.29
CADD
Pathogenic
35
DANN
Uncertain
0.97
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.26
N
PhyloP100
2.7
Vest4
0.69
GERP RS
4.2
Mutation Taster
=10/190
disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs4941543; hg19: chr13-46708291; API