11-1884518-C-T

Variant names:

• chr11-1884518-C-T
• rs183535747
• NM_002339.3:c.654C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002339.3(LSP1):​c.654C>T​(p.Ser218Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S218S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LSP1 NM_002339.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-0.591 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002339.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSP1	NM_002339.3	MANE Select	c.654C>T	p.Ser218Ser	synonymous	Exon 7 of 11	NP_002330.1	P33241-1
	LSP1	NM_001242932.2		c.1038C>T	p.Ser346Ser	synonymous	Exon 8 of 12	NP_001229861.1	P33241-3
	LSP1	NM_001013253.2		c.468C>T	p.Ser156Ser	synonymous	Exon 7 of 11	NP_001013271.1	P33241-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSP1	ENST00000311604.8	TSL:1 MANE Select	c.654C>T	p.Ser218Ser	synonymous	Exon 7 of 11	ENSP00000308383.4	P33241-1
	LSP1	ENST00000381775.5	TSL:2	c.1038C>T	p.Ser346Ser	synonymous	Exon 8 of 12	ENSP00000371194.1	P33241-3
	LSP1	ENST00000962912.1		c.681C>T	p.Ser227Ser	synonymous	Exon 7 of 11	ENSP00000632971.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461756 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111936

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.3
DANN	Benign	0.57
PhyloP100		-0.59

Splicing

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

Other links and lift over

dbSNP: rs183535747; hg19: chr11-1905748;