rs115705313

Variant names:

• chr1-47416226-G-C
• rs115705313
• ENST00000828805.1:n.207+17137C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-47416226-G-C
• chr1-47416226-G-T

Variant summary

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

The NR_126355.1(LINC01389):​n.29-6325C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 942,524 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: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: LINC01389 NR_126355.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• 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: AR, AD Classification: DEFINITIVE Submitted by: G2P
• congenital primary aphakia

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• 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, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• anterior segment dysgenesis

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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: 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.29-6325C>G		intron	N/A
	FOXE3	NM_012186.3	MANE Select	c.-90G>C		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+17137C>G		intron	N/A
	LINC01389	ENST00000828806.1		n.92+1005C>G		intron	N/A
	LINC01389	ENST00000828807.1		n.92+1005C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 151212 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000979

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000379 AC: 3 AN: 791312 Hom.: 0 Cov.: 10 AF XY: 0.00000263 AC XY: 1 AN XY: 380162

African (AFR) AF: 0.00 AC: 0 AN: 15648

American (AMR) AF: 0.00 AC: 0 AN: 5434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9296

East Asian (EAS) AF: 0.00 AC: 0 AN: 19602

South Asian (SAS) AF: 0.00 AC: 0 AN: 18950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2112

European-Non Finnish (NFE) AF: 0.00000446 AC: 3 AN: 671940

Other (OTH) AF: 0.00 AC: 0 AN: 30752

GnomAD4 genome AF: 0.0000265 AC: 4 AN: 151212 Hom.: 0 Cov.: 31 AF XY: 0.0000406 AC XY: 3 AN XY: 73842

African (AFR) AF: 0.0000979 AC: 4 AN: 40862

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5064

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67848

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		1.0
PromoterAI		0.074	Neutral

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: rs115705313; hg19: chr1-47881898;