11-1881538-G-C

Variant names:

• chr11-1881538-G-C
• rs621679
• NM_002339.3:c.298G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001242932.2(LSP1):​c.682G>C​(p.Ala228Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: LSP1 NM_001242932.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 35 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041499376).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242932.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSP1	NM_002339.3	MANE Select	c.298G>C	p.Ala100Pro	missense	Exon 3 of 11	NP_002330.1
	LSP1	NM_001242932.2		c.682G>C	p.Ala228Pro	missense	Exon 4 of 12	NP_001229861.1
	LSP1	NM_001013253.2		c.112G>C	p.Ala38Pro	missense	Exon 3 of 11	NP_001013271.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSP1	ENST00000311604.8	TSL:1 MANE Select	c.298G>C	p.Ala100Pro	missense	Exon 3 of 11	ENSP00000308383.4
	LSP1	ENST00000381775.5	TSL:2	c.682G>C	p.Ala228Pro	missense	Exon 4 of 12	ENSP00000371194.1
	LSP1	ENST00000962912.1		c.298G>C	p.Ala100Pro	missense	Exon 3 of 11	ENSP00000632971.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.017
DANN	Benign	0.63
DEOGEN2	Benign	0.081	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.9
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.087
Sift	Benign	0.043	D
Sift4G	Benign	0.27	T
Polyphen		0.0030	B
Vest4		0.034
MutPred		0.10		Loss of loop (P = 0.1242)
MVP		0.18
MPC		0.14
ClinPred		0.096	T
GERP RS		-6.0
Varity_R		0.19
gMVP		0.031
Mutation Taster		=89/11	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs621679; hg19: chr11-1902768;