rs621679

chr11-1881538-G-Achr11-1881538-G-C

Variant summary

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

The NM_002339.3(LSP1):c.298G>A(p.Ala100Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,545,222 control chromosomes in the GnomAD database, including 112,979 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (10853 hom., cov: 34)
  • Exomes 𝑓: 0.38 (102126 hom.)
• Consequence: LSP1 NM_002339.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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 (MetaRNN=1.4315276E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LSP1	NM_002339.3	c.298G>A	p.Ala100Thr	missense_variant	3/11	ENST00000311604.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSP1	ENST00000311604.8	c.298G>A	p.Ala100Thr	missense_variant	3/11	1	NM_002339.3	P2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55663 AN: 150852 Hom.: 10847 Cov.: 34

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.382

GnomAD3 exomes AF: 0.410 AC: 62454 AN: 152148 Hom.: 13901 AF XY: 0.398 AC XY: 32032 AN XY: 80476

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.589

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.581

Gnomad SAS exome AF: 0.275

Gnomad FIN exome AF: 0.419

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.399

GnomAD4 exome AF: 0.377 AC: 525881 AN: 1394252 Hom.: 102126 Cov.: 51 AF XY: 0.374 AC XY: 257321 AN XY: 687746

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.579

Gnomad4 ASJ exome AF: 0.365

Gnomad4 EAS exome AF: 0.563

Gnomad4 SAS exome AF: 0.279

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.374

Gnomad4 OTH exome AF: 0.374

GnomAD4 genome AF: 0.369 AC: 55699 AN: 150970 Hom.: 10853 Cov.: 34 AF XY: 0.372 AC XY: 27418 AN XY: 73744

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.381

Alfa AF: 0.372 Hom.: 5188

Bravo AF: 0.377

TwinsUK AF: 0.358 AC: 1328

ALSPAC AF: 0.363 AC: 1400

ESP6500AA AF: 0.267 AC: 1155

ESP6500EA AF: 0.362 AC: 3046

ExAC AF: 0.297 AC: 30181

Asia WGS AF: 0.446 AC: 1542 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.0050
Dann	Benign	0.26
DEOGEN2	Benign	0.044	T;.;T;.;.;T;.;.;T;.;.;T;T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.48	T;T;T;T;.;T;T;T;T;.;T;.;T
MetaRNN	Benign	0.000014	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.29	N;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.97	N;N;N;N;N;N;N;N;N;N;.;N;N
REVEL	Benign	0.054
Sift	Benign	1.0	T;T;T;T;T;T;T;T;T;T;.;T;T
Sift4G	Benign	0.71	T;T;T;T;T;T;T;.;T;T;T;T;T
Polyphen		0.010	B;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.0090
MPC		0.10
ClinPred		0.0018	T
GERP RS		-6.0
Varity_R		0.036
gMVP		0.021

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs621679; hg19: chr11-1902768; COSMIC: COSV61132084; COSMIC: COSV61132084;