Variant rs17853500 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002345.4(LUM):c.507T>C(p.Asn169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,614,026 control chromosomes in the GnomAD database, including 2,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 250 hom., cov: 32)

Exomes 𝑓: 0.031 ( 1873 hom. )

Consequence

LUM
NM_002345.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.05

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 12-91108473-A-G is Benign according to our data. Variant chr12-91108473-A-G is described in ClinVar as [Benign]. Clinvar id is 1275250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LUM	NM_002345.4 linkuse as main transcript	c.507T>C	p.Asn169=	synonymous_variant	2/3	ENST00000266718.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LUM	ENST00000266718.5 linkuse as main transcript	c.507T>C	p.Asn169=	synonymous_variant	2/3	1	NM_002345.4	P1
LUM	ENST00000546642.1 linkuse as main transcript	n.257T>C		non_coding_transcript_exon_variant	2/3	3
LUM	ENST00000548071.1 linkuse as main transcript	n.90-190T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

4739

AN:

152086

Hom.:

249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0397

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.0906

Gnomad FIN

AF:

0.0198

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.0522

AC:

13094

AN:

250934

Hom.:

940

AF XY:

0.0522

AC XY:

7075

AN XY:

135578

show subpopulations

Gnomad AFR exome

AF:

0.0141

Gnomad AMR exome

AF:

0.0568

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.270

Gnomad SAS exome

AF:

0.0849

Gnomad FIN exome

AF:

0.0233

Gnomad NFE exome

AF:

0.0214

Gnomad OTH exome

AF:

0.0415

GnomAD4 exome

AF:

0.0306

AC:

44767

AN:

1461822

Hom.:

1873

Cov.:

AF XY:

0.0319

AC XY:

23209

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0133

Gnomad4 AMR exome

AF:

0.0556

Gnomad4 ASJ exome

AF:

0.0174

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.0817

Gnomad4 FIN exome

AF:

0.0246

Gnomad4 NFE exome

AF:

0.0191

Gnomad4 OTH exome

AF:

0.0403

GnomAD4 genome

AF:

0.0312

AC:

4744

AN:

152204

Hom.:

250

Cov.:

AF XY:

0.0344

AC XY:

2561

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0156

Gnomad4 AMR

AF:

0.0396

Gnomad4 ASJ

AF:

0.0185

Gnomad4 EAS

AF:

0.261

Gnomad4 SAS

AF:

0.0909

Gnomad4 FIN

AF:

0.0198

Gnomad4 NFE

AF:

0.0197

Gnomad4 OTH

AF:

0.0313

Alfa

AF:

0.0207

Hom.:

Bravo

AF:

0.0323

Asia WGS

AF:

0.169

AC:

586

AN:

3478

EpiCase

AF:

0.0212

EpiControl

AF:

0.0190

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

LUM-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

3.8

DANN

Benign

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over