12-91109269-C-CTT

Position:

• chr12-91109269-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002345.4(LUM):​c.-21-270_-21-269insAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.96 (70516 hom., cov: 0)
• Consequence: LUM NM_002345.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.491

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-91109269-C-CTT is Benign according to our data. Variant chr12-91109269-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1282615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LUM	NM_002345.4	c.-21-270_-21-269insAA		intron_variant		ENST00000266718.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LUM	ENST00000266718.5	c.-21-270_-21-269insAA		intron_variant		1	NM_002345.4	P1
LUM	ENST00000546642.1	n.43-583_43-582insAA		intron_variant, non_coding_transcript_variant		3
LUM	ENST00000548071.1	n.90-987_90-986insAA		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146345 AN: 152016 Hom.: 70471 Cov.: 0

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.964

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

GnomAD4 genome AF: 0.963 AC: 146448 AN: 152134 Hom.: 70516 Cov.: 0 AF XY: 0.964 AC XY: 71658 AN XY: 74342

Gnomad4 AFR AF: 0.942

Gnomad4 AMR AF: 0.976

Gnomad4 ASJ AF: 0.974

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.990

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.966

Gnomad4 OTH AF: 0.964

Alfa AF: 0.963 Hom.: 7575

Asia WGS AF: 0.994 AC: 3456 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3071441; hg19: chr12-91503046;