rs3168534

Positions:

• chr12-91103516-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000266718.5(LUM):​c.*649T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 152,132 control chromosomes in the GnomAD database, including 574 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 0.078 (574 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LUM ENST00000266718.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

Genes affected

LUM (HGNC:6724): (lumican) This gene encodes a member of the small leucine-rich proteoglycan (SLRP) family that includes decorin, biglycan, fibromodulin, keratocan, epiphycan, and osteoglycin. In these bifunctional molecules, the protein moiety binds collagen fibrils and the highly charged hydrophilic glycosaminoglycans regulate interfibrillar spacings. Lumican is the major keratan sulfate proteoglycan of the cornea but is also distributed in interstitial collagenous matrices throughout the body. Lumican may regulate collagen fibril organization and circumferential growth, corneal transparency, and epithelial cell migration and tissue repair. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LUM	NM_002345.4	c.*649T>C		3_prime_UTR_variant	3/3	ENST00000266718.5	NP_002336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUM	ENST00000266718.5	c.*649T>C		3_prime_UTR_variant	3/3	1	NM_002345.4	ENSP00000266718	P1

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11793 AN: 152014 Hom.: 572 Cov.: 33

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.0989

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0403

Gnomad FIN AF: 0.0724

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0905

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0775 AC: 11797 AN: 152132 Hom.: 574 Cov.: 33 AF XY: 0.0765 AC XY: 5689 AN XY: 74370

Gnomad4 AFR AF: 0.0293

Gnomad4 AMR AF: 0.0898

Gnomad4 ASJ AF: 0.0989

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0408

Gnomad4 FIN AF: 0.0724

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0900

Alfa AF: 0.110 Hom.: 886

Bravo AF: 0.0765

Asia WGS AF: 0.0230 AC: 80 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.46

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: rs3168534; hg19: chr12-91497293;