12-91111527-A-AGG

Variant names:

• chr12-91111527-A-AGG
• rs3832846
• NM_002345.4:c.-152_-151insCC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002345.4(LUM):​c.-152_-151insCC variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.88 (58033 hom., cov: 0)
  • Exomes 𝑓: 0.92 (15 hom.)
• Consequence: LUM NM_002345.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360
• Publications: 3 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUM	NM_002345.4	c.-152_-151insCC		upstream_gene_variant		ENST00000266718.5	NP_002336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LUM	ENST00000266718.5	c.-152_-151insCC		upstream_gene_variant		1	NM_002345.4	ENSP00000266718.4
LUM	ENST00000546642.1	n.-89_-88insCC		upstream_gene_variant		3
LUM	ENST00000548071.1	n.-42_-41insCC		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.883 AC: 131252 AN: 148596 Hom.: 58013 Cov.: 0

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.885

GnomAD4 exome AF: 0.917 AC: 33 AN: 36 Hom.: 15 Cov.: 0 AF XY: 0.923 AC XY: 24 AN XY: 26

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.906 AC: 29 AN: 32

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.883 AC: 131317 AN: 148704 Hom.: 58033 Cov.: 0 AF XY: 0.881 AC XY: 63914 AN XY: 72518

African (AFR) AF: 0.794 AC: 31318 AN: 39438

American (AMR) AF: 0.857 AC: 12820 AN: 14956

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3280 AN: 3444

East Asian (EAS) AF: 0.733 AC: 3689 AN: 5030

South Asian (SAS) AF: 0.882 AC: 4175 AN: 4736

European-Finnish (FIN) AF: 0.953 AC: 9741 AN: 10224

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.939 AC: 63474 AN: 67610

Other (OTH) AF: 0.885 AC: 1834 AN: 2072

Alfa AF: 0.906 Hom.: 1974

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3832846; hg19: chr12-91505304; COSMIC: COSV57127385; COSMIC: COSV57127385;