rs11105988

Variant names:

• chr12-91104522-T-A
• rs11105988
• NM_002345.4:c.863-203A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUM	NM_002345.4	MANE Select	c.863-203A>T		intron	N/A	NP_002336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUM	ENST00000266718.5	TSL:1 MANE Select	c.863-203A>T		intron	N/A	ENSP00000266718.4
	LUM	ENST00000891369.1		c.863-203A>T		intron	N/A	ENSP00000561428.1
	LUM	ENST00000963638.1		c.863-203A>T		intron	N/A	ENSP00000633697.1

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

African (AFR) AF: 0.299 AC: 12396 AN: 41448

American (AMR) AF: 0.139 AC: 2112 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3468

East Asian (EAS) AF: 0.0554 AC: 287 AN: 5178

South Asian (SAS) AF: 0.0573 AC: 277 AN: 4830

European-Finnish (FIN) AF: 0.0869 AC: 921 AN: 10598

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.131 AC: 8903 AN: 67978

Other (OTH) AF: 0.167 AC: 353 AN: 2114

Alfa AF: 0.159 Hom.: 274

Bravo AF: 0.183

Asia WGS AF: 0.0690 AC: 241 AN: 3462

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.79
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11105988; hg19: chr12-91498299;