12-91104422-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002345.4(LUM):​c.863-103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 782,242 control chromosomes in the GnomAD database, including 3,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1071 hom., cov: 32)
  • Exomes 𝑓: 0.075 (2005 hom.)
• Consequence: LUM NM_002345.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-91104422-C-T is Benign according to our data. Variant chr12-91104422-C-T is described in ClinVar as Benign. ClinVar VariationId is 1181470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUM	NM_002345.4	c.863-103G>A		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.863-103G>A		intron_variant	Intron 2 of 2	1	NM_002345.4	ENSP00000266718.4
LUM	ENST00000546642.1	n.613-103G>A		intron_variant	Intron 2 of 2	3
LUM	ENST00000548071.1	n.256-103G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15970 AN: 151862 Hom.: 1068 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0524

Gnomad SAS AF: 0.0406

Gnomad FIN AF: 0.0497

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.0981

GnomAD4 exome AF: 0.0749 AC: 47232 AN: 630262 Hom.: 2005 AF XY: 0.0735 AC XY: 24375 AN XY: 331540

African (AFR) AF: 0.175 AC: 2676 AN: 15292

American (AMR) AF: 0.0555 AC: 1051 AN: 18936

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 2453 AN: 16144

East Asian (EAS) AF: 0.0568 AC: 1780 AN: 31322

South Asian (SAS) AF: 0.0442 AC: 2092 AN: 47352

European-Finnish (FIN) AF: 0.0541 AC: 1776 AN: 32806

Middle Eastern (MID) AF: 0.0959 AC: 225 AN: 2346

European-Non Finnish (NFE) AF: 0.0749 AC: 32551 AN: 434374

Other (OTH) AF: 0.0829 AC: 2628 AN: 31690

GnomAD4 genome AF: 0.105 AC: 15995 AN: 151980 Hom.: 1071 Cov.: 32 AF XY: 0.102 AC XY: 7562 AN XY: 74290

African (AFR) AF: 0.185 AC: 7687 AN: 41474

American (AMR) AF: 0.0761 AC: 1159 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3470

East Asian (EAS) AF: 0.0523 AC: 271 AN: 5178

South Asian (SAS) AF: 0.0404 AC: 195 AN: 4824

European-Finnish (FIN) AF: 0.0497 AC: 525 AN: 10556

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.0782 AC: 5312 AN: 67938

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.0879 Hom.: 381

Bravo AF: 0.111

Asia WGS AF: 0.0510 AC: 177 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.17
PhyloP100		0.35
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: rs17018718; hg19: chr12-91498199;