Variant 12-91104422-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002345.4(LUM):c.863-103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 782,242 control chromosomes in the GnomAD database, including 3,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1071 hom., cov: 32)

Exomes 𝑓: 0.075 ( 2005 hom. )

Consequence

LUM
NM_002345.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.354

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-91104422-C-T is Benign according to our data. Variant chr12-91104422-C-T is described in ClinVar as [Benign]. Clinvar id is 1181470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 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.863-103G>A		intron_variant		ENST00000266718.5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
LUM	ENST00000266718.5 linkuse as main transcript	c.863-103G>A	intron_variant	1	NM_002345.4	P1
LUM	ENST00000546642.1 linkuse as main transcript	n.613-103G>A	intron_variant, non_coding_transcript_variant	3
LUM	ENST00000548071.1 linkuse as main transcript	n.256-103G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15970

AN:

151862

Hom.:

1068

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0762

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.0524

Gnomad SAS

AF:

0.0406

Gnomad FIN

AF:

0.0497

Gnomad MID

AF:

0.118

Gnomad NFE

AF:

0.0782

Gnomad OTH

AF:

0.0981

GnomAD4 exome

AF:

0.0749

AC:

47232

AN:

630262

Hom.:

2005

AF XY:

0.0735

AC XY:

24375

AN XY:

331540

show subpopulations

Gnomad4 AFR exome

AF:

0.175

Gnomad4 AMR exome

AF:

0.0555

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.0568

Gnomad4 SAS exome

AF:

0.0442

Gnomad4 FIN exome

AF:

0.0541

Gnomad4 NFE exome

AF:

0.0749

Gnomad4 OTH exome

AF:

0.0829

GnomAD4 genome

AF:

0.105

AC:

15995

AN:

151980

Hom.:

1071

Cov.:

AF XY:

0.102

AC XY:

7562

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.0761

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.0523

Gnomad4 SAS

AF:

0.0404

Gnomad4 FIN

AF:

0.0497

Gnomad4 NFE

AF:

0.0782

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.0863

Hom.:

336

Bravo

AF:

0.111

Asia WGS

AF:

0.0510

AC:

177

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

DANN

Benign

0.17

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