chr11-1881538-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242932.2(LSP1):​c.682G>A​(p.Ala228Thr) 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. 14/20 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: 𝑓 0.37 (10853 hom., cov: 34)
  • Exomes 𝑓: 0.38 (102126 hom.)
• 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: Benign. The variant received -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.

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>A	p.Ala100Thr	missense	Exon 3 of 11	NP_002330.1
	LSP1	NM_001242932.2		c.682G>A	p.Ala228Thr	missense	Exon 4 of 12	NP_001229861.1
	LSP1	NM_001013253.2		c.112G>A	p.Ala38Thr	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>A	p.Ala100Thr	missense	Exon 3 of 11	ENSP00000308383.4
	LSP1	ENST00000381775.5	TSL:2	c.682G>A	p.Ala228Thr	missense	Exon 4 of 12	ENSP00000371194.1
	LSP1	ENST00000962912.1		c.298G>A	p.Ala100Thr	missense	Exon 3 of 11	ENSP00000632971.1

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

GnomAD2 exomes AF: 0.410 AC: 62454 AN: 152148 AF XY: 0.398

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 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

African (AFR) AF: 0.262 AC: 8255 AN: 31486

American (AMR) AF: 0.579 AC: 20320 AN: 35074

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 9042 AN: 24768

East Asian (EAS) AF: 0.563 AC: 20335 AN: 36144

South Asian (SAS) AF: 0.279 AC: 21962 AN: 78784

European-Finnish (FIN) AF: 0.418 AC: 20312 AN: 48634

Middle Eastern (MID) AF: 0.364 AC: 1992 AN: 5470

European-Non Finnish (NFE) AF: 0.374 AC: 402116 AN: 1076248

Other (OTH) AF: 0.374 AC: 21547 AN: 57644

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

African (AFR) AF: 0.271 AC: 11232 AN: 41388

American (AMR) AF: 0.506 AC: 7680 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1244 AN: 3432

East Asian (EAS) AF: 0.576 AC: 2955 AN: 5128

South Asian (SAS) AF: 0.304 AC: 1455 AN: 4786

European-Finnish (FIN) AF: 0.420 AC: 4375 AN: 10428

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25439 AN: 67340

Other (OTH) AF: 0.381 AC: 800 AN: 2100

Alfa AF: 0.378 Hom.: 7581

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 v4.9

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
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.000014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.29	N
PhyloP100		-1.9
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.97	N
REVEL	Benign	0.054
Sift	Benign	1.0	T
Sift4G	Benign	0.71	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
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV61132084; COSMIC: COSV61132084;