Genetic Variant LCP1:c.-25+9117A>G (chr13-46172994-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002298.5(LCP1):c.-25+9117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,102 control chromosomes in the GnomAD database, including 2,649 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2649 hom., cov: 32)

Consequence

LCP1
NM_002298.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.767

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
LCP1	NM_002298.5 link	c.-25+9117A>G	intron_variant	Intron 1 of 15	ENST00000323076.7	NP_002289.2
LCP1	XM_005266374.3 link	c.-4556A>G	5_prime_UTR_variant	Exon 1 of 16		XP_005266431.1
LCP1	XM_047430305.1 link	c.-25+9117A>G	intron_variant	Intron 1 of 8		XP_047286261.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
LCP1	ENST00000323076.7 link	c.-25+9117A>G	intron_variant	Intron 1 of 15	1	NM_002298.5	ENSP00000315757.2
LCP1	ENST00000398576.6 link	c.-25+9117A>G	intron_variant	Intron 4 of 18	5		ENSP00000381581.1
LCP1	ENST00000442275.1 link	c.-25+9117A>G	intron_variant	Intron 5 of 6	3		ENSP00000402157.1
LCP1	ENST00000460190.1 link	n.94+9117A>G	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26842

AN:

151986

Hom.:

2643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.177

AC:

26873

AN:

152102

Hom.:

2649

Cov.:

AF XY:

0.176

AC XY:

13097

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.146

AC:

6052

AN:

41504

American (AMR)

AF:

0.206

AC:

3148

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

847

AN:

3468

East Asian (EAS)

AF:

0.342

AC:

1765

AN:

5156

South Asian (SAS)

AF:

0.264

AC:

1274

AN:

4824

European-Finnish (FIN)

AF:

0.101

AC:

1076

AN:

10602

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.178

AC:

12082

AN:

67966

Other (OTH)

AF:

0.214

AC:

452

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1127

2254

3382

4509

5636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.183

Hom.:

1512

Bravo

AF:

0.184

Asia WGS

AF:

0.294

AC:

1021

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.75

(source)

DANN

Benign

0.47

PhyloP100

-0.77

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over