12-91104422-C-A

Variant names:

• chr12-91104422-C-A
• rs17018718
• NM_002345.4:c.863-103G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002345.4(LUM):​c.863-103G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 630,806 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: LUM NM_002345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUM	NM_002345.4	MANE Select	c.863-103G>T		intron	N/A	NP_002336.1	P51884

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUM	ENST00000266718.5	TSL:1 MANE Select	c.863-103G>T		intron	N/A	ENSP00000266718.4	P51884
	LUM	ENST00000891369.1		c.863-103G>T		intron	N/A	ENSP00000561428.1
	LUM	ENST00000963638.1		c.863-103G>T		intron	N/A	ENSP00000633697.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000159 AC: 1 AN: 630806 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 331784

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15326

American (AMR) AF: 0.00 AC: 0 AN: 18942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16164

East Asian (EAS) AF: 0.00 AC: 0 AN: 31328

South Asian (SAS) AF: 0.00 AC: 0 AN: 47382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2348

European-Non Finnish (NFE) AF: 0.00000230 AC: 1 AN: 434776

Other (OTH) AF: 0.00 AC: 0 AN: 31706

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.98
DANN	Benign	0.22
PhyloP100		0.35

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: rs17018718; hg19: chr12-91498199;