chr11-1853174-C-T

Variant names:

• chr11-1853174-C-T
• rs2089910
• NM_002339.3:c.30C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002339.3(LSP1):​c.30C>T​(p.Ala10Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,610,092 control chromosomes in the GnomAD database, including 48,041 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. Synonymous variant affecting the same amino acid position (i.e. A10A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.26 (5433 hom., cov: 33)
  • Exomes 𝑓: 0.24 (42608 hom.)
• Consequence: LSP1 NM_002339.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.96
• Publications: 28 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-3.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

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.30C>T	p.Ala10Ala	synonymous	Exon 1 of 11	NP_002330.1	P33241-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSP1	ENST00000311604.8	TSL:1 MANE Select	c.30C>T	p.Ala10Ala	synonymous	Exon 1 of 11	ENSP00000308383.4	P33241-1
	LSP1	ENST00000962912.1		c.30C>T	p.Ala10Ala	synonymous	Exon 1 of 11	ENSP00000632971.1
	LSP1	ENST00000861224.1		c.30C>T	p.Ala10Ala	synonymous	Exon 2 of 12	ENSP00000531283.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39723 AN: 151968 Hom.: 5439 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.265

GnomAD2 exomes AF: 0.258 AC: 61511 AN: 238024 AF XY: 0.253

Gnomad AFR exome AF: 0.280

Gnomad AMR exome AF: 0.281

Gnomad ASJ exome AF: 0.232

Gnomad EAS exome AF: 0.467

Gnomad FIN exome AF: 0.278

Gnomad NFE exome AF: 0.230

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.237 AC: 346169 AN: 1458006 Hom.: 42608 Cov.: 34 AF XY: 0.236 AC XY: 171463 AN XY: 725058

African (AFR) AF: 0.286 AC: 9566 AN: 33462

American (AMR) AF: 0.285 AC: 12549 AN: 44048

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 6019 AN: 25902

East Asian (EAS) AF: 0.444 AC: 17548 AN: 39530

South Asian (SAS) AF: 0.192 AC: 16432 AN: 85604

European-Finnish (FIN) AF: 0.279 AC: 14695 AN: 52596

Middle Eastern (MID) AF: 0.273 AC: 1561 AN: 5720

European-Non Finnish (NFE) AF: 0.228 AC: 253194 AN: 1110928

Other (OTH) AF: 0.243 AC: 14605 AN: 60216

GnomAD4 genome AF: 0.261 AC: 39743 AN: 152086 Hom.: 5433 Cov.: 33 AF XY: 0.265 AC XY: 19706 AN XY: 74354

African (AFR) AF: 0.276 AC: 11436 AN: 41474

American (AMR) AF: 0.275 AC: 4209 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3470

East Asian (EAS) AF: 0.464 AC: 2392 AN: 5152

South Asian (SAS) AF: 0.201 AC: 971 AN: 4820

European-Finnish (FIN) AF: 0.288 AC: 3045 AN: 10574

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16016 AN: 67976

Other (OTH) AF: 0.264 AC: 557 AN: 2112

Alfa AF: 0.245 Hom.: 13427

Bravo AF: 0.265

Asia WGS AF: 0.312 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.6
DANN	Benign	0.73
PhyloP100		-4.0
PromoterAI		-0.11	Neutral
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: rs2089910; hg19: chr11-1874404; COSMIC: COSV61138446;