Variant 12-91108680-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_002345.4(LUM):c.300C>T(p.Asn100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,613,714 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 13 hom. )

Consequence

LUM
NM_002345.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.138

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 12-91108680-G-A is Benign according to our data. Variant chr12-91108680-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038362.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.138 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LUM	NM_002345.4 linkuse as main transcript	c.300C>T	p.Asn100=	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.300C>T	p.Asn100=	synonymous_variant	2/3	1	NM_002345.4	P1
LUM	ENST00000546642.1 linkuse as main transcript	n.50C>T		non_coding_transcript_exon_variant	2/3	3
LUM	ENST00000548071.1 linkuse as main transcript	n.90-397C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

286

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00323

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00162

AC:

407

AN:

250632

Hom.:

AF XY:

0.00160

AC XY:

217

AN XY:

135416

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.00311

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00328

AC:

4787

AN:

1461512

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

2241

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000861

Gnomad4 NFE exome

AF:

0.00403

Gnomad4 OTH exome

AF:

0.00323

GnomAD4 genome

AF:

0.00188

AC:

286

AN:

152202

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

118

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000747

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00323

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00258

Hom.:

Bravo

AF:

0.00202

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00344

EpiControl

AF:

0.00480

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LUM-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 06, 2019

This variant is classified as likely 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

-0.56

CADD

Benign

4.6

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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