rs2089910

Positions:

• chr11-1853174-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.96

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LSP1	NM_002339.3	c.30C>T	p.Ala10Ala	synonymous_variant	1/11	ENST00000311604.8	NP_002330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSP1	ENST00000311604.8	c.30C>T	p.Ala10Ala	synonymous_variant	1/11	1	NM_002339.3	ENSP00000308383.4
LSP1	ENST00000676039.1	c.30C>T	p.Ala10Ala	synonymous_variant	2/2			ENSP00000502383.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39723 AN: 151968 Hom.: 5439 Cov.: 33

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

GnomAD3 exomes AF: 0.258 AC: 61511 AN: 238024 Hom.: 8431 AF XY: 0.253 AC XY: 32742 AN XY: 129260

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 SAS exome AF: 0.193

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.: 34 AF XY: 0.236 AC XY: 171463 AN XY: 725058

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.261 AC: 39743 AN: 152086 Hom.: 5433 Cov.: 33 AF XY: 0.265 AC XY: 19706 AN XY: 74354

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.264

Alfa AF: 0.241 Hom.: 8214

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
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2089910; hg19: chr11-1874404; COSMIC: COSV61138446;