11-58571651-T-C

Position:

• chr11-58571651-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPXN	NM_004811.3	c.14-938A>G		intron_variant		ENST00000395074.7	NP_004802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPXN	ENST00000395074.7	c.14-938A>G		intron_variant		1	NM_004811.3	ENSP00000378512	A2

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

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.198

Alfa AF: 0.224 Hom.: 3807

Bravo AF: 0.186

Asia WGS AF: 0.239 AC: 822 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.11
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs10896794; hg19: chr11-58339124;