chr12-91105258-G-C

Variant names:

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

Variant summary

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

The NM_002345.4(LUM):​c.863-939C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,060 control chromosomes in the GnomAD database, including 54,443 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 0.85 (54443 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUM	NM_002345.4	c.863-939C>G		intron_variant	Intron 2 of 2	ENST00000266718.5	NP_002336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LUM	ENST00000266718.5	c.863-939C>G		intron_variant	Intron 2 of 2	1	NM_002345.4	ENSP00000266718.4
LUM	ENST00000546642.1	n.613-939C>G		intron_variant	Intron 2 of 2	3
LUM	ENST00000548071.1	n.256-939C>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128502 AN: 151942 Hom.: 54404 Cov.: 30

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.846 AC: 128595 AN: 152060 Hom.: 54443 Cov.: 30 AF XY: 0.845 AC XY: 62791 AN XY: 74328

African (AFR) AF: 0.864 AC: 35841 AN: 41478

American (AMR) AF: 0.846 AC: 12915 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3017 AN: 3472

East Asian (EAS) AF: 0.737 AC: 3796 AN: 5152

South Asian (SAS) AF: 0.860 AC: 4137 AN: 4810

European-Finnish (FIN) AF: 0.891 AC: 9445 AN: 10602

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56795 AN: 67958

Other (OTH) AF: 0.838 AC: 1767 AN: 2108

Alfa AF: 0.840 Hom.: 6267

Bravo AF: 0.844

Asia WGS AF: 0.789 AC: 2745 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		-0.017
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: rs10745553; hg19: chr12-91499035;