Genetic Variant LUM:c.-231C>T (chr12-91111607-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002345.4(LUM):c.-231C>T variant causes a upstream gene change. The variant allele was found at a frequency of 0.0298 in 152,298 control chromosomes in the GnomAD database, including 243 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 0.030 ( 243 hom., cov: 32)

Exomes 𝑓: 0.071 ( 0 hom. )

Consequence

LUM
NM_002345.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.45

Publications

8 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUM	NM_002345.4 link	c.-231C>T		upstream_gene_variant		ENST00000266718.5	NP_002336.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein
LUM	ENST00000266718.5 link	c.-231C>T	upstream_gene_variant	1	NM_002345.4	ENSP00000266718.4
LUM	ENST00000546642.1 link	n.-168C>T	upstream_gene_variant	3
LUM	ENST00000548071.1 link	n.-121C>T	upstream_gene_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

4539

AN:

152124

Hom.:

244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0394

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.0903

Gnomad FIN

AF:

0.0198

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.0321

GnomAD4 exome

AF:

0.0714

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0952

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0238

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.588

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0298

AC:

4535

AN:

152242

Hom.:

243

Cov.:

AF XY:

0.0329

AC XY:

2450

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0110

AC:

456

AN:

41560

American (AMR)

AF:

0.0393

AC:

600

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3470

East Asian (EAS)

AF:

0.260

AC:

1340

AN:

5156

South Asian (SAS)

AF:

0.0906

AC:

437

AN:

4826

European-Finnish (FIN)

AF:

0.0198

AC:

210

AN:

10614

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0197

AC:

1341

AN:

68024

Other (OTH)

AF:

0.0313

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

217

433

650

866

1083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0278

Hom.:

134

Bravo

AF:

0.0309

Asia WGS

AF:

0.166

AC:

576

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

4.5

PromoterAI

-0.068

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over