rs661348

Positions:

• chr11-1884062-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002339.3(LSP1):​c.591+38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,574,862 control chromosomes in the GnomAD database, including 141,011 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 0.38 (12094 hom., cov: 31)
  • Exomes 𝑓: 0.42 (128917 hom.)
• Consequence: LSP1 NM_002339.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LSP1	NM_002339.3	c.591+38T>C		intron_variant		ENST00000311604.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSP1	ENST00000311604.8	c.591+38T>C		intron_variant		1	NM_002339.3	P2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57192 AN: 151472 Hom.: 12088 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.383

GnomAD3 exomes AF: 0.429 AC: 99337 AN: 231588 Hom.: 22986 AF XY: 0.419 AC XY: 52431 AN XY: 125224

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.384

Gnomad EAS exome AF: 0.596

Gnomad SAS exome AF: 0.272

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.425

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.419 AC: 596287 AN: 1423284 Hom.: 128917 Cov.: 26 AF XY: 0.414 AC XY: 293113 AN XY: 707510

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.405

GnomAD4 genome AF: 0.377 AC: 57215 AN: 151578 Hom.: 12094 Cov.: 31 AF XY: 0.382 AC XY: 28255 AN XY: 74030

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.380

Alfa AF: 0.417 Hom.: 16154

Bravo AF: 0.376

Asia WGS AF: 0.459 AC: 1594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
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: rs661348; hg19: chr11-1905292; COSMIC: COSV61135122; COSMIC: COSV61135122;