rs17169429

Variant names:

• chr5-135936789-A-G
• rs17169429
• ENST00000467490.5:n.106-15A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000522943.5(LECT2):​c.290-14355T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,367,592 control chromosomes in the GnomAD database, including 290 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 0.030 (163 hom., cov: 32)
  • Exomes 𝑓: 0.0080 (127 hom.)
• Consequence: LECT2 ENST00000522943.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477

Genes affected

FBXL21P (HGNC:13600): (F-box and leucine rich repeat protein 21, pseudogene) This locus represents a transcribed pseudogene that is related to genes encoding members of the F-box family of proteins. [provided by RefSeq, Nov 2017]

LECT2 (HGNC:6550): (leukocyte cell derived chemotaxin 2) This gene encodes a secreted, 16 kDa protein that acts as a chemotactic factor to neutrophils and stimulates the growth of chondrocytes and osteoblasts. This protein has high sequence similarity to the chondromodulin repeat regions of the chicken myb-induced myeloid 1 protein. A polymorphism in this gene may be associated with rheumatoid arthritis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL21P	NR_152420.1	n.595A>G		non_coding_transcript_exon_variant	Exon 4 of 6
FBXL21P	NR_152421.1	n.599A>G		non_coding_transcript_exon_variant	Exon 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL21P	ENST00000467490.5	n.106-15A>G		intron_variant	Intron 2 of 6	1
LECT2	ENST00000522943.5	c.290-14355T>C		intron_variant	Intron 3 of 3	3		ENSP00000429618.1
FBXL21P	ENST00000297158.11	n.277A>G		non_coding_transcript_exon_variant	Exon 2 of 5	6

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 4577 AN: 152122 Hom.: 162 Cov.: 32

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00733

Gnomad OTH AF: 0.0292

GnomAD3 exomes AF: 0.0123 AC: 3054 AN: 249140 Hom.: 64 AF XY: 0.0106 AC XY: 1434 AN XY: 135142

Gnomad AFR exome AF: 0.0839

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.00954

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00128

Gnomad FIN exome AF: 0.0157

Gnomad NFE exome AF: 0.00746

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.00804 AC: 9768 AN: 1215352 Hom.: 127 Cov.: 31 AF XY: 0.00759 AC XY: 4574 AN XY: 602312

Gnomad4 AFR exome AF: 0.0857

Gnomad4 AMR exome AF: 0.0112

Gnomad4 ASJ exome AF: 0.00965

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00127

Gnomad4 FIN exome AF: 0.0148

Gnomad4 NFE exome AF: 0.00600

Gnomad4 OTH exome AF: 0.0107

GnomAD4 genome AF: 0.0302 AC: 4592 AN: 152240 Hom.: 163 Cov.: 32 AF XY: 0.0295 AC XY: 2193 AN XY: 74426

Gnomad4 AFR AF: 0.0848

Gnomad4 AMR AF: 0.0182

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0155

Gnomad4 NFE AF: 0.00734

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0181 Hom.: 42

Bravo AF: 0.0334

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	0.17
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17169429; hg19: chr5-135272478;