Variant 13-46158935-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002298.5(LCP1):c.119C>T(p.Ala40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00721 in 1,614,104 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 50 hom. )

Consequence

LCP1
NM_002298.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.37

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007674128).

BP6

Variant 13-46158935-G-A is Benign according to our data. Variant chr13-46158935-G-A is described in ClinVar as [Benign]. Clinvar id is 718752.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 750 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP1	NM_002298.5 linkuse as main transcript	c.119C>T	p.Ala40Val	missense_variant	3/16	ENST00000323076.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP1	ENST00000323076.7 linkuse as main transcript	c.119C>T	p.Ala40Val	missense_variant	3/16	1	NM_002298.5	P1	P13796-1
CPB2-AS1	ENST00000663159.1 linkuse as main transcript	n.1031G>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.00493

AC:

750

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00689

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00521

AC:

1311

AN:

251436

Hom.:

AF XY:

0.00508

AC XY:

690

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00989

Gnomad NFE exome

AF:

0.00777

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00745

AC:

10885

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00726

AC XY:

5283

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00490

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.00972

Gnomad4 NFE exome

AF:

0.00863

Gnomad4 OTH exome

AF:

0.00677

GnomAD4 genome

AF:

0.00493

AC:

750

AN:

152282

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

367

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.00689

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00645

Hom.:

Bravo

AF:

0.00453

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00802

AC:

ExAC

AF:

0.00534

AC:

648

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00676

EpiControl

AF:

0.00800

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T;.;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.86

MetaRNN

Benign

0.0077

T;T;T;T

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.6

M;M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.0

N;N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.24

T;T;T;D

Polyphen

0.45

B;B;.;.

Vest4

0.14

MVP

0.54

MPC

0.40

ClinPred

0.059

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.62

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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