13-46130931-T-C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_002298.5(LCP1):c.1634A>G(p.Lys545Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,604,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

LCP1
NM_002298.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

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 made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28520525).

BS2

High AC in GnomAdExome4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP1	NM_002298.5 link	c.1634A>G	p.Lys545Arg	missense_variant	Exon 15 of 16	ENST00000323076.7	NP_002289.2	P13796-1A0A024RDT4
LCP1	XM_005266374.3 link	c.1634A>G	p.Lys545Arg	missense_variant	Exon 15 of 16		XP_005266431.1	P13796-1A0A024RDT4
LCP1	XM_047430303.1 link	c.1634A>G	p.Lys545Arg	missense_variant	Exon 15 of 16		XP_047286259.1
LCP1	XM_047430304.1 link	c.1199A>G	p.Lys400Arg	missense_variant	Exon 13 of 14		XP_047286260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LCP1	ENST00000323076.7 link	c.1634A>G	p.Lys545Arg	missense_variant	Exon 15 of 16	1	NM_002298.5	ENSP00000315757.2	P13796-1
LCP1	ENST00000398576.6 link	c.1634A>G	p.Lys545Arg	missense_variant	Exon 18 of 19	5		ENSP00000381581.1	P13796-1
LCP1	ENST00000674665.1 link	c.341A>G	p.Lys114Arg	missense_variant	Exon 4 of 5			ENSP00000501964.1	P13796-2
CPB2-AS1	ENST00000663159.1 link	n.470-20563T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000167

AC:

AN:

239252

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

129688

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000353

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000296

AC:

AN:

1452214

Hom.:

Cov.:

AF XY:

0.0000318

AC XY:

AN XY:

722190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000379

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1634A>G (p.K545R) alteration is located in exon 15 (coding exon 14) of the LCP1 gene. This alteration results from a A to G substitution at nucleotide position 1634, causing the lysine (K) at amino acid position 545 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Uncertain

0.62

D;D

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.051

MetaRNN

Benign

0.29

T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.27

Sift

Benign

0.080

T;T

Sift4G

Uncertain

0.046

D;D

Polyphen

0.023

B;B

Vest4

0.070

MutPred

0.40

Loss of ubiquitination at K545 (P = 0.0127);Loss of ubiquitination at K545 (P = 0.0127);

MVP

0.64

MPC

0.33

ClinPred

0.058

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.097

gMVP

0.31

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over