Genetic Variant LSP1:p.Ala10Ala (chr11-1853174-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002339.3(LSP1):c.30C>T(p.Ala10Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,610,092 control chromosomes in the GnomAD database, including 48,041 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 0.26 ( 5433 hom., cov: 33)

Exomes 𝑓: 0.24 ( 42608 hom. )

Consequence

LSP1
NM_002339.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.96

Publications

28 publications found

Variant links:

Genes affected

LSP1 (HGNC:6707): (lymphocyte specific protein 1) This gene encodes an intracellular F-actin binding protein. The protein is expressed in lymphocytes, neutrophils, macrophages, and endothelium and may regulate neutrophil motility, adhesion to fibrinogen matrix proteins, and transendothelial migration. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

LSP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP7

Synonymous conserved (PhyloP=-3.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSP1	NM_002339.3 link	c.30C>T	p.Ala10Ala	synonymous_variant	Exon 1 of 11	ENST00000311604.8	NP_002330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSP1	ENST00000311604.8 link	c.30C>T	p.Ala10Ala	synonymous_variant	Exon 1 of 11	1	NM_002339.3	ENSP00000308383.4
LSP1	ENST00000676039.1 link	c.30C>T	p.Ala10Ala	synonymous_variant	Exon 2 of 2			ENSP00000502383.1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39723

AN:

151968

Hom.:

5439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.465

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.265

GnomAD2 exomes

AF:

0.258

AC:

61511

AN:

238024

AF XY:

0.253

show subpopulations

Gnomad AFR exome

AF:

0.280

Gnomad AMR exome

AF:

0.281

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.278

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.237

AC:

346169

AN:

1458006

Hom.:

42608

Cov.:

AF XY:

0.236

AC XY:

171463

AN XY:

725058

show subpopulations

African (AFR)

AF:

0.286

AC:

9566

AN:

33462

American (AMR)

AF:

0.285

AC:

12549

AN:

44048

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

6019

AN:

25902

East Asian (EAS)

AF:

0.444

AC:

17548

AN:

39530

South Asian (SAS)

AF:

0.192

AC:

16432

AN:

85604

European-Finnish (FIN)

AF:

0.279

AC:

14695

AN:

52596

Middle Eastern (MID)

AF:

0.273

AC:

1561

AN:

5720

European-Non Finnish (NFE)

AF:

0.228

AC:

253194

AN:

1110928

Other (OTH)

AF:

0.243

AC:

14605

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

14010

28020

42031

56041

70051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8778

17556

26334

35112

43890

<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:

0.261

AC:

39743

AN:

152086

Hom.:

5433

Cov.:

AF XY:

0.265

AC XY:

19706

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.276

AC:

11436

AN:

41474

American (AMR)

AF:

0.275

AC:

4209

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

821

AN:

3470

East Asian (EAS)

AF:

0.464

AC:

2392

AN:

5152

South Asian (SAS)

AF:

0.201

AC:

971

AN:

4820

European-Finnish (FIN)

AF:

0.288

AC:

3045

AN:

10574

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.236

AC:

16016

AN:

67976

Other (OTH)

AF:

0.264

AC:

557

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1520

3041

4561

6082

7602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.245

Hom.:

13427

Bravo

AF:

0.265

Asia WGS

AF:

0.312

AC:

1085

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.6

(source)

DANN

Benign

0.73

PhyloP100

-4.0

PromoterAI

-0.11

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over