11-58571651-T-C

Variant names:

• chr11-58571651-T-C
• rs10896794
• NM_004811.3:c.14-938A>G

Variant summary

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

The NM_004811.3(LPXN):​c.14-938A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 149,598 control chromosomes in the GnomAD database, including 3,095 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.

• Frequency: Genomes: 𝑓 0.20 (3095 hom., cov: 31)
• Consequence: LPXN NM_004811.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• Publications: 33 publications found

Genes affected

LPXN (HGNC:14061): (leupaxin) The product encoded by this gene is preferentially expressed in hematopoietic cells and belongs to the paxillin protein family. Similar to other members of this focal-adhesion-associated adaptor-protein family, it has four leucine-rich LD-motifs in the N-terminus and four LIM domains in the C-terminus. It may function in cell type-specific signaling by associating with PYK2, a member of focal adhesion kinase family. As a substrate for a tyrosine kinase in lymphoid cells, this protein may also function in, and be regulated by, tyrosine kinase activity. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004811.3. 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
	LPXN	NM_004811.3	MANE Select	c.14-938A>G		intron	N/A	NP_004802.1
	LPXN	NM_001143995.3		c.29-938A>G		intron	N/A	NP_001137467.1
	LPXN	NM_001307951.2		c.1-938A>G		intron	N/A	NP_001294880.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPXN	ENST00000395074.7	TSL:1 MANE Select	c.14-938A>G		intron	N/A	ENSP00000378512.2
	LPXN	ENST00000530561.5	TSL:1	n.14-938A>G		intron	N/A	ENSP00000437094.1
	LPXN	ENST00000528954.5	TSL:2	c.29-938A>G		intron	N/A	ENSP00000431284.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29415 AN: 149504 Hom.: 3093 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.197 AC: 29424 AN: 149598 Hom.: 3095 Cov.: 31 AF XY: 0.198 AC XY: 14504 AN XY: 73074

African (AFR) AF: 0.125 AC: 5118 AN: 40816

American (AMR) AF: 0.180 AC: 2717 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3466

East Asian (EAS) AF: 0.181 AC: 930 AN: 5148

South Asian (SAS) AF: 0.266 AC: 1274 AN: 4786

European-Finnish (FIN) AF: 0.252 AC: 2392 AN: 9474

Middle Eastern (MID) AF: 0.309 AC: 87 AN: 282

European-Non Finnish (NFE) AF: 0.229 AC: 15481 AN: 67570

Other (OTH) AF: 0.198 AC: 413 AN: 2082

Alfa AF: 0.220 Hom.: 9358

Bravo AF: 0.186

Asia WGS AF: 0.239 AC: 822 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.11
DANN	Benign	0.56
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10896794; hg19: chr11-58339124;