rs3168534

Variant names:

• chr12-91103516-A-G
• rs3168534
• NM_002345.4:c.*649T>C

Variant summary

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

The NM_002345.4(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 NM_002345.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002345.4. 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
	LUM	NM_002345.4	MANE Select	c.*649T>C		3_prime_UTR	Exon 3 of 3	NP_002336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUM	ENST00000266718.5	TSL:1 MANE Select	c.*649T>C		3_prime_UTR	Exon 3 of 3	ENSP00000266718.4
	LUM	ENST00000548071.1	TSL:3	n.*67T>C		downstream_gene	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0293 AC: 1217 AN: 41556

American (AMR) AF: 0.0898 AC: 1370 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0989 AC: 343 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5190

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4830

European-Finnish (FIN) AF: 0.0724 AC: 768 AN: 10612

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7570 AN: 67908

Other (OTH) AF: 0.0900 AC: 190 AN: 2110

Alfa AF: 0.108 Hom.: 996

Bravo AF: 0.0765

Asia WGS AF: 0.0230 AC: 80 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		1.2
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: rs3168534; hg19: chr12-91497293;