1-47416272-C-T

Variant names:

• chr1-47416272-C-T
• rs188265445
• ENST00000828805.1:n.207+17091G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NR_126355.1(LINC01389):​n.29-6371G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,241,872 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (41 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (23 hom.)
• Consequence: LINC01389 NR_126355.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.791
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-47416272-C-T is Benign according to our data. Variant chr1-47416272-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1204109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0116 (1754/151698) while in subpopulation AFR AF = 0.0399 (1656/41504). AF 95% confidence interval is 0.0383. There are 41 homozygotes in GnomAd4. There are 822 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 gene

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.29-6371G>A		intron	N/A
	FOXE3	NM_012186.3	MANE Select	c.-44C>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+17091G>A		intron	N/A
	LINC01389	ENST00000828806.1		n.92+959G>A		intron	N/A
	LINC01389	ENST00000828807.1		n.92+959G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1751 AN: 151588 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000222

Gnomad OTH AF: 0.00675

GnomAD2 exomes AF: 0.00158 AC: 5 AN: 3158 AF XY: 0.00150

Gnomad AFR exome AF: 0.0455

Gnomad AMR exome AF: 0.00227

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.0182

GnomAD4 exome AF: 0.00101 AC: 1096 AN: 1090174 Hom.: 23 Cov.: 23 AF XY: 0.000889 AC XY: 466 AN XY: 524298

African (AFR) AF: 0.0371 AC: 813 AN: 21924

American (AMR) AF: 0.00384 AC: 31 AN: 8080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13584

East Asian (EAS) AF: 0.00 AC: 0 AN: 25084

South Asian (SAS) AF: 0.0000318 AC: 1 AN: 31466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21558

Middle Eastern (MID) AF: 0.00209 AC: 6 AN: 2868

European-Non Finnish (NFE) AF: 0.000120 AC: 111 AN: 922828

Other (OTH) AF: 0.00313 AC: 134 AN: 42782

GnomAD4 genome AF: 0.0116 AC: 1754 AN: 151698 Hom.: 41 Cov.: 32 AF XY: 0.0111 AC XY: 822 AN XY: 74116

African (AFR) AF: 0.0399 AC: 1656 AN: 41504

American (AMR) AF: 0.00438 AC: 67 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000222 AC: 15 AN: 67598

Other (OTH) AF: 0.00668 AC: 14 AN: 2096

Alfa AF: 0.0100 Hom.: 4

Bravo AF: 0.0130

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Uncertain	0.98
PhyloP100		0.79
PromoterAI		-0.024	Neutral
Mutation Taster		=280/20	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: rs188265445; hg19: chr1-47881944;