12-91111068-A-G

Variant names:

• chr12-91111068-A-G
• rs10859110
• NM_002345.4:c.-22+330T>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.-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
• Publications: 6 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=-0.81).
• 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 rank	MANE	Protein	UniProt
LUM	NM_002345.4	c.-22+330T>C		intron_variant	Intron 1 of 2	ENST00000266718.5	NP_002336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LUM	ENST00000266718.5	c.-22+330T>C		intron_variant	Intron 1 of 2	1	NM_002345.4	ENSP00000266718.4
LUM	ENST00000546642.1	n.42+330T>C		intron_variant	Intron 1 of 2	3
LUM	ENST00000548071.1	n.89+330T>C		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.266 AC: 11021 AN: 41488

American (AMR) AF: 0.665 AC: 10137 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2408 AN: 3470

East Asian (EAS) AF: 0.611 AC: 3152 AN: 5158

South Asian (SAS) AF: 0.783 AC: 3775 AN: 4820

European-Finnish (FIN) AF: 0.836 AC: 8840 AN: 10570

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51004 AN: 67958

Other (OTH) AF: 0.624 AC: 1318 AN: 2112

Alfa AF: 0.713 Hom.: 62977

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
PhyloP100		0.087
PromoterAI		-0.0059	Neutral
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: rs10859110; hg19: chr12-91504845; COSMIC: COSV57129021;