chr1-47416235-TGGG-T

Variant names:

• chr1-47416235-TGGG-T
• rs137862650
• ENST00000828805.1:n.207+17125_207+17127delCCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NR_126355.1(LINC01389):​n.29-6337_29-6335delCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 800,688 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: LINC01389 NR_126355.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

Genes affected

LINC01389 (HGNC:50661): (long intergenic non-protein coding RNA 1389)

FOXE3 (HGNC:3808): (forkhead box E3) This intronless gene belongs to the forkhead family of transcription factors, which is characterized by a distinct forkhead domain. The protein encoded functions as a lens-specific transcription factor and plays an important role in vertebrate lens formation. Mutations in this gene are associated with anterior segment mesenchymal dysgenesis and congenital primary aphakia. [provided by RefSeq, Dec 2009]

FOXE3 Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AD, AR Classification: DEFINITIVE Submitted by: G2P
• congenital primary aphakia

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• anterior segment dysgenesis 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• aortic aneurysm, familial thoracic 11, susceptibility to

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• anterior segment dysgenesis

  Inheritance: Unknown, AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: Unknown, AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Peters anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_126355.1. 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
	LINC01389	NR_126355.1		n.29-6337_29-6335delCCC		intron	N/A
	FOXE3	NM_012186.3	MANE Select	c.-80_-78delGGG		upstream_gene	N/A	NP_036318.1	Q13461

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC01389	ENST00000828805.1		n.207+17125_207+17127delCCC		intron	N/A
	LINC01389	ENST00000828806.1		n.92+993_92+995delCCC		intron	N/A
	LINC01389	ENST00000828807.1		n.92+993_92+995delCCC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000125 AC: 1 AN: 800688 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 382900

⚠️ 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: 15430

American (AMR) AF: 0.00 AC: 0 AN: 4816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8654

East Asian (EAS) AF: 0.00 AC: 0 AN: 17416

South Asian (SAS) AF: 0.00 AC: 0 AN: 19436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2002

European-Non Finnish (NFE) AF: 0.00000145 AC: 1 AN: 688122

Other (OTH) AF: 0.00 AC: 0 AN: 30054

⚠️ 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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

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: rs137862650; hg19: chr1-47881907;