chr12-91111068-A-G

Position:

• chr12-91111068-A-G

Variant summary

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

The NM_002345.4(LUM):​c.-22+330T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,024 control chromosomes in the GnomAD database, including 31,686 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 0.61 (31686 hom., cov: 31)
• Consequence: LUM NM_002345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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]

LUM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LUM	NM_002345.4	c.-22+330T>C		intron_variant		ENST00000266718.5	NP_002336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUM	ENST00000266718.5	c.-22+330T>C		intron_variant		1	NM_002345.4	ENSP00000266718.4
LUM	ENST00000546642.1	n.42+330T>C		intron_variant		3
LUM	ENST00000548071.1	n.89+330T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92430 AN: 151906 Hom.: 31688 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.608 AC: 92435 AN: 152024 Hom.: 31686 Cov.: 31 AF XY: 0.614 AC XY: 45616 AN XY: 74284

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.836

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.624

Alfa AF: 0.717 Hom.: 53241

Bravo AF: 0.577

Asia WGS AF: 0.653 AC: 2257 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
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: rs10859110; hg19: chr12-91504845; COSMIC: COSV57129021;