chr12-91105258-G-A

Variant names:

• chr12-91105258-G-A
• rs10745553
• NM_002345.4:c.863-939C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002345.4(LUM):​c.863-939C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: LUM NM_002345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.863-939C>T		intron	N/A	NP_002336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUM	ENST00000266718.5	TSL:1 MANE Select	c.863-939C>T		intron	N/A	ENSP00000266718.4
	LUM	ENST00000546642.1	TSL:3	n.613-939C>T		intron	N/A
	LUM	ENST00000548071.1	TSL:3	n.256-939C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 6267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		-0.017

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: rs10745553; hg19: chr12-91499035;