rs2300588

Positions:

• chr12-91106120-C-A
• chr12-91106120-C-G

Variant summary

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

The NM_002345.4(LUM):​c.863-1801G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 152,230 control chromosomes in the GnomAD database, including 62,896 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 0.91 (62896 hom., cov: 32)
• Consequence: LUM NM_002345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LUM	NM_002345.4	c.863-1801G>T		intron_variant		ENST00000266718.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LUM	ENST00000266718.5	c.863-1801G>T		intron_variant		1	NM_002345.4	P1
LUM	ENST00000546642.1	n.613-1801G>T		intron_variant, non_coding_transcript_variant		3
LUM	ENST00000548071.1	n.256-1801G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.907 AC: 137998 AN: 152112 Hom.: 62869 Cov.: 32

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.953

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.902

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

GnomAD4 genome AF: 0.907 AC: 138079 AN: 152230 Hom.: 62896 Cov.: 32 AF XY: 0.905 AC XY: 67363 AN XY: 74408

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.902

Gnomad4 ASJ AF: 0.953

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.943

Gnomad4 OTH AF: 0.903

Alfa AF: 0.935 Hom.: 60901

Bravo AF: 0.900

Asia WGS AF: 0.776 AC: 2697 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.57

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: rs2300588; hg19: chr12-91499897;