12-91111607-G-A

Variant names:

• chr12-91111607-G-A
• rs3741834
• NM_002345.4:c.-231C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002345.4(LUM):​c.-231C>T variant causes a upstream gene change. The variant allele was found at a frequency of 0.0298 in 152,298 control chromosomes in the GnomAD database, including 243 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (243 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: LUM NM_002345.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 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.-231C>T		upstream_gene	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.-231C>T		upstream_gene	N/A	ENSP00000266718.4
	LUM	ENST00000546642.1	TSL:3	n.-168C>T		upstream_gene	N/A
	LUM	ENST00000548071.1	TSL:3	n.-121C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4539 AN: 152124 Hom.: 244 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0394

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0903

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0321

GnomAD4 exome AF: 0.0714 AC: 4 AN: 56 Hom.: 0 Cov.: 0 AF XY: 0.0952 AC XY: 4 AN XY: 42

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0238 AC: 1 AN: 42

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.0298 AC: 4535 AN: 152242 Hom.: 243 Cov.: 32 AF XY: 0.0329 AC XY: 2450 AN XY: 74406

African (AFR) AF: 0.0110 AC: 456 AN: 41560

American (AMR) AF: 0.0393 AC: 600 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1340 AN: 5156

South Asian (SAS) AF: 0.0906 AC: 437 AN: 4826

European-Finnish (FIN) AF: 0.0198 AC: 210 AN: 10614

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0197 AC: 1341 AN: 68024

Other (OTH) AF: 0.0313 AC: 66 AN: 2110

Alfa AF: 0.0278 Hom.: 134

Bravo AF: 0.0309

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.84
PhyloP100		4.5
PromoterAI		-0.068	Neutral
Mutation Taster		=300/0	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: rs3741834; hg19: chr12-91505384;