dbSNP rs11478: LUM:c.*625G>A (chr12-91103540-C-T) – 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.*625G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 152,090 control chromosomes in the GnomAD database, including 576 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 0.078 ( 576 hom., cov: 33)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

LUM
NM_002345.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

Publications

4 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=-0.52).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002345.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUM	NM_002345.4	MANE Select	c.*625G>A		3_prime_UTR	Exon 3 of 3	NP_002336.1	P51884

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LUM	ENST00000266718.5	TSL:1 MANE Select	c.*625G>A	3_prime_UTR	Exon 3 of 3	ENSP00000266718.4	P51884
LUM	ENST00000891369.1		c.*625G>A	downstream_gene	N/A	ENSP00000561428.1
LUM	ENST00000963638.1		c.*625G>A	downstream_gene	N/A	ENSP00000633697.1

Frequencies

GnomAD3 genomes

AF:

0.0780

AC:

11847

AN:

151964

Hom.:

574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0304

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.0900

Gnomad ASJ

AF:

0.0988

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0400

Gnomad FIN

AF:

0.0728

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.0908

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0779

AC:

11853

AN:

152082

Hom.:

576

Cov.:

AF XY:

0.0769

AC XY:

5720

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0304

AC:

1261

AN:

41546

American (AMR)

AF:

0.0902

AC:

1377

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0988

AC:

343

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5184

South Asian (SAS)

AF:

0.0404

AC:

195

AN:

4826

European-Finnish (FIN)

AF:

0.0728

AC:

771

AN:

10586

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7571

AN:

67890

Other (OTH)

AF:

0.0913

AC:

193

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

572

1145

1717

2290

2862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.0674

Hom.:

120

Bravo

AF:

0.0769

Asia WGS

AF:

0.0320

AC:

111

AN:

3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

1.1

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over