rs11105988

Positions:

• chr12-91104522-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002345.4(LUM):​c.863-203A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,060 control chromosomes in the GnomAD database, including 2,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2793 hom., cov: 32)
• Consequence: LUM NM_002345.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-91104522-T-A is Benign according to our data. Variant chr12-91104522-T-A is described in ClinVar as [Benign]. Clinvar id is 1224049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LUM	NM_002345.4	c.863-203A>T		intron_variant		ENST00000266718.5	NP_002336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUM	ENST00000266718.5	c.863-203A>T		intron_variant		1	NM_002345.4	ENSP00000266718	P1
LUM	ENST00000546642.1	n.613-203A>T		intron_variant, non_coding_transcript_variant		3
LUM	ENST00000548071.1	n.256-203A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26022 AN: 151940 Hom.: 2780 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0555

Gnomad SAS AF: 0.0575

Gnomad FIN AF: 0.0869

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.164

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.171 AC: 26067 AN: 152060 Hom.: 2793 Cov.: 32 AF XY: 0.165 AC XY: 12281 AN XY: 74330

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.0554

Gnomad4 SAS AF: 0.0573

Gnomad4 FIN AF: 0.0869

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.167

Alfa AF: 0.159 Hom.: 274

Bravo AF: 0.183

Asia WGS AF: 0.0690 AC: 241 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.86
CADD	Benign	1.0
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs11105988; hg19: chr12-91498299;