NM_002298.5:c.1597A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002298.5(LCP1):c.1597A>G(p.Lys533Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 1,613,158 control chromosomes in the GnomAD database, including 661,210 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. K533R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.87 ( 58436 hom., cov: 31)

Exomes 𝑓: 0.91 ( 602774 hom. )

Consequence

LCP1
NM_002298.5 missense

Scores

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]

LCP1 links:

CPB2-AS1 (HGNC:39898): (CPB2 antisense RNA 1)

CPB2-AS1 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 (MetaRNN=8.141835E-7).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP1	NM_002298.5 link	c.1597A>G	p.Lys533Glu	missense_variant	Exon 14 of 16	ENST00000323076.7	NP_002289.2	P13796-1A0A024RDT4
LCP1	XM_005266374.3 link	c.1597A>G	p.Lys533Glu	missense_variant	Exon 14 of 16		XP_005266431.1	P13796-1A0A024RDT4
LCP1	XM_047430303.1 link	c.1597A>G	p.Lys533Glu	missense_variant	Exon 14 of 16		XP_047286259.1
LCP1	XM_047430304.1 link	c.1162A>G	p.Lys388Glu	missense_variant	Exon 12 of 14		XP_047286260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LCP1	ENST00000323076.7 link	c.1597A>G	p.Lys533Glu	missense_variant	Exon 14 of 16	1	NM_002298.5	ENSP00000315757.2	P13796-1
LCP1	ENST00000398576.6 link	c.1597A>G	p.Lys533Glu	missense_variant	Exon 17 of 19	5		ENSP00000381581.1	P13796-1
LCP1	ENST00000674665.1 link	c.304A>G	p.Lys102Glu	missense_variant	Exon 3 of 5			ENSP00000501964.1	P13796-2
CPB2-AS1	ENST00000663159.1 link	n.470-17338T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.875

AC:

132999

AN:

152068

Hom.:

58394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.785

Gnomad AMI

AF:

0.905

Gnomad AMR

AF:

0.912

Gnomad ASJ

AF:

0.894

Gnomad EAS

AF:

0.911

Gnomad SAS

AF:

0.966

Gnomad FIN

AF:

0.934

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.900

Gnomad OTH

AF:

0.883

GnomAD2 exomes

AF:

0.910

AC:

228767

AN:

251298

AF XY:

0.913

show subpopulations

Gnomad AFR exome

AF:

0.783

Gnomad AMR exome

AF:

0.954

Gnomad ASJ exome

AF:

0.895

Gnomad EAS exome

AF:

0.899

Gnomad FIN exome

AF:

0.934

Gnomad NFE exome

AF:

0.899

Gnomad OTH exome

AF:

0.914

GnomAD4 exome

AF:

0.908

AC:

1326456

AN:

1460972

Hom.:

602774

Cov.:

AF XY:

0.909

AC XY:

660998

AN XY:

726846

show subpopulations

African (AFR)

AF:

0.794

AC:

26560

AN:

33444

American (AMR)

AF:

0.952

AC:

42565

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.893

AC:

23340

AN:

26128

East Asian (EAS)

AF:

0.930

AC:

36897

AN:

39658

South Asian (SAS)

AF:

0.966

AC:

83328

AN:

86244

European-Finnish (FIN)

AF:

0.932

AC:

49691

AN:

53328

Middle Eastern (MID)

AF:

0.911

AC:

5248

AN:

5760

European-Non Finnish (NFE)

AF:

0.904

AC:

1004166

AN:

1111324

Other (OTH)

AF:

0.905

AC:

54661

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

5569

11137

16706

22274

27843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21462

42924

64386

85848

107310

<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:

0.875

AC:

133100

AN:

152186

Hom.:

58436

Cov.:

AF XY:

0.879

AC XY:

65370

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.785

AC:

32573

AN:

41474

American (AMR)

AF:

0.912

AC:

13946

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.894

AC:

3103

AN:

3472

East Asian (EAS)

AF:

0.911

AC:

4714

AN:

5176

South Asian (SAS)

AF:

0.966

AC:

4664

AN:

4826

European-Finnish (FIN)

AF:

0.934

AC:

9910

AN:

10614

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.900

AC:

61240

AN:

68012

Other (OTH)

AF:

0.885

AC:

1871

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

827

1654

2480

3307

4134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.893

Hom.:

205679

Bravo

AF:

0.868

TwinsUK

AF:

0.898

AC:

3328

ALSPAC

AF:

0.905

AC:

3488

ESP6500AA

AF:

0.798

AC:

3517

ESP6500EA

AF:

0.903

AC:

7762

ExAC

AF:

0.906

AC:

109959

Asia WGS

AF:

0.931

AC:

3233

AN:

3478

EpiCase

AF:

0.898

EpiControl

AF:

0.898

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Uncertain

0.47

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.19

.;T

MetaRNN

Benign

8.1e-7

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-0.35

N;N

PhyloP100

2.7

PrimateAI

Benign

0.27

PROVEAN

Benign

0.17

N;N

REVEL

Uncertain

0.29

Sift

Benign

0.10

T;T

Sift4G

Benign

0.099

T;T

Polyphen

0.0

B;B

Vest4

0.031

MPC

0.49

ClinPred

0.0076

GERP RS

4.2

Varity_R

0.10

gMVP

0.48

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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