1-47416226-G-T

Variant names:

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

Variant summary

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

The NR_126355.1(LINC01389):​n.29-6325C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 942,146 control chromosomes in the GnomAD database, including 1,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (111 hom., cov: 31)
  • Exomes 𝑓: 0.044 (897 hom.)
• Consequence: LINC01389 NR_126355.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-47416226-G-T is Benign according to our data. Variant chr1-47416226-G-T is described in ClinVar as Benign. ClinVar VariationId is 1296404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0502 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.29-6325C>A		intron	N/A
	FOXE3	NM_012186.3	MANE Select	c.-90G>T		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>A		intron	N/A
	LINC01389	ENST00000828806.1		n.92+1005C>A		intron	N/A
	LINC01389	ENST00000828807.1		n.92+1005C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0332 AC: 5016 AN: 151200 Hom.: 111 Cov.: 31

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.000395

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.0429

GnomAD4 exome AF: 0.0444 AC: 35112 AN: 790838 Hom.: 897 Cov.: 10 AF XY: 0.0440 AC XY: 16706 AN XY: 379934

African (AFR) AF: 0.00601 AC: 94 AN: 15648

American (AMR) AF: 0.0310 AC: 168 AN: 5428

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 177 AN: 9296

East Asian (EAS) AF: 0.0000510 AC: 1 AN: 19602

South Asian (SAS) AF: 0.00296 AC: 56 AN: 18950

European-Finnish (FIN) AF: 0.0356 AC: 626 AN: 17570

Middle Eastern (MID) AF: 0.0142 AC: 30 AN: 2112

European-Non Finnish (NFE) AF: 0.0489 AC: 32862 AN: 671490

Other (OTH) AF: 0.0357 AC: 1098 AN: 30742

GnomAD4 genome AF: 0.0331 AC: 5015 AN: 151308 Hom.: 111 Cov.: 31 AF XY: 0.0309 AC XY: 2288 AN XY: 73958

African (AFR) AF: 0.0105 AC: 431 AN: 40980

American (AMR) AF: 0.0349 AC: 533 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0211 AC: 73 AN: 3462

East Asian (EAS) AF: 0.000396 AC: 2 AN: 5048

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4826

European-Finnish (FIN) AF: 0.0320 AC: 339 AN: 10588

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0516 AC: 3499 AN: 67832

Other (OTH) AF: 0.0424 AC: 89 AN: 2098

Alfa AF: 0.0278 Hom.: 17

Bravo AF: 0.0323

Asia WGS AF: 0.00260 AC: 9 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		1.0
PromoterAI		-0.024	Neutral
Mutation Taster		=300/0	polymorphism

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; COSMIC: COSV58633350;