1-47416235-TGGGGG-TGGGGGG

Variant names:

• chr1-47416235-T-TG
• rs137862650
• ENST00000828805.1:n.207+17127_207+17128insC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NR_126355.1(LINC01389):​n.29-6335dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 934,374 control chromosomes in the GnomAD database, including 404 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (296 hom., cov: 31)
  • Exomes 𝑓: 0.018 (108 hom.)
• Consequence: LINC01389 NR_126355.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.312
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-47416235-T-TG is Benign according to our data. Variant chr1-47416235-T-TG is described in ClinVar as Benign. ClinVar VariationId is 1228957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

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.29-6335dupC		intron	N/A
	FOXE3	NM_012186.3	MANE Select	c.-81_-80insG		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+17127_207+17128insC		intron	N/A
	LINC01389	ENST00000828806.1		n.92+995_92+996insC		intron	N/A
	LINC01389	ENST00000828807.1		n.92+995_92+996insC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6434 AN: 142578 Hom.: 295 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00116

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0178

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.00515

Gnomad MID AF: 0.0400

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0382

GnomAD4 exome AF: 0.0183 AC: 14477 AN: 791726 Hom.: 108 Cov.: 12 AF XY: 0.0179 AC XY: 6793 AN XY: 378650

African (AFR) AF: 0.108 AC: 1638 AN: 15232

American (AMR) AF: 0.0278 AC: 133 AN: 4776

Ashkenazi Jewish (ASJ) AF: 0.0259 AC: 221 AN: 8540

East Asian (EAS) AF: 0.144 AC: 2477 AN: 17210

South Asian (SAS) AF: 0.0159 AC: 306 AN: 19220

European-Finnish (FIN) AF: 0.0116 AC: 170 AN: 14636

Middle Eastern (MID) AF: 0.0258 AC: 51 AN: 1978

European-Non Finnish (NFE) AF: 0.0128 AC: 8697 AN: 680410

Other (OTH) AF: 0.0264 AC: 784 AN: 29724

GnomAD4 genome AF: 0.0451 AC: 6437 AN: 142648 Hom.: 296 Cov.: 31 AF XY: 0.0444 AC XY: 3084 AN XY: 69454

African (AFR) AF: 0.114 AC: 4431 AN: 38892

American (AMR) AF: 0.0311 AC: 448 AN: 14406

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 59 AN: 3316

East Asian (EAS) AF: 0.122 AC: 574 AN: 4710

South Asian (SAS) AF: 0.0124 AC: 54 AN: 4344

European-Finnish (FIN) AF: 0.00515 AC: 47 AN: 9130

Middle Eastern (MID) AF: 0.0435 AC: 12 AN: 276

European-Non Finnish (NFE) AF: 0.0114 AC: 738 AN: 64734

Other (OTH) AF: 0.0369 AC: 73 AN: 1980

Alfa AF: 0.00301 Hom.: 1

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.31
Mutation Taster		=300/0	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: rs137862650; hg19: chr1-47881907; COSMIC: COSV58632500;