rs2268578

Variant names:

• chr12-91107421-A-G
• rs2268578
• NM_002345.4:c.862+697T>C

Variant summary

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

The NM_002345.4(LUM):​c.862+697T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,348 control chromosomes in the GnomAD database, including 42,752 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 0.72 (42752 hom., cov: 28)
• Consequence: LUM NM_002345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 13 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUM	NM_002345.4	c.862+697T>C		intron_variant	Intron 2 of 2	ENST00000266718.5	NP_002336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LUM	ENST00000266718.5	c.862+697T>C		intron_variant	Intron 2 of 2	1	NM_002345.4	ENSP00000266718.4
LUM	ENST00000546642.1	n.612+697T>C		intron_variant	Intron 2 of 2	3
LUM	ENST00000548071.1	n.255+697T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.720 AC: 108906 AN: 151230 Hom.: 42748 Cov.: 28

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.720 AC: 108933 AN: 151348 Hom.: 42752 Cov.: 28 AF XY: 0.724 AC XY: 53546 AN XY: 73954

African (AFR) AF: 0.376 AC: 15480 AN: 41158

American (AMR) AF: 0.797 AC: 12115 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2770 AN: 3462

East Asian (EAS) AF: 0.680 AC: 3443 AN: 5060

South Asian (SAS) AF: 0.848 AC: 4053 AN: 4778

European-Finnish (FIN) AF: 0.911 AC: 9571 AN: 10504

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 58996 AN: 67874

Other (OTH) AF: 0.756 AC: 1587 AN: 2100

Alfa AF: 0.811 Hom.: 36442

Bravo AF: 0.693

Asia WGS AF: 0.715 AC: 2450 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		0.18
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: rs2268578; hg19: chr12-91501198;