Genetic Variant LINC01389:n.29-6344G>C (chr1-47416245-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NR_126355.1(LINC01389):n.29-6344G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,088,402 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 63 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 15 hom. )

Consequence

LINC01389
NR_126355.1 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.344

Variant links:

Genes affected

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

LINC01389 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-47416245-C-G is Benign according to our data. Variant chr1-47416245-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1217846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (2224/151486) while in subpopulation AFR AF= 0.0508 (2091/41138). AF 95% confidence interval is 0.049. There are 63 homozygotes in gnomad4. There are 1014 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 63 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC01389	NR_126355.1 link	n.29-6344G>C		intron_variant	Intron 1 of 4
FOXE3	NM_012186.3 link	c.-71C>G		upstream_gene_variant		ENST00000335071.4	NP_036318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXE3	ENST00000335071.4 link	c.-71C>G		upstream_gene_variant		6	NM_012186.3	ENSP00000334472.2		Q13461

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2218

AN:

151372

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00590

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00968

Gnomad NFE

AF:

0.000310

Gnomad OTH

AF:

0.00817

GnomAD4 exome

AF:

0.00133

AC:

1248

AN:

936916

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

548

AN XY:

448836

show subpopulations

Gnomad4 AFR exome

AF:

0.0485

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000822

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000272

Gnomad4 OTH exome

AF:

0.00299

GnomAD4 genome

AF:

0.0147

AC:

2224

AN:

151486

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1014

AN XY:

74042

show subpopulations

Gnomad4 AFR

AF:

0.0508

Gnomad4 AMR

AF:

0.00589

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000310

Gnomad4 OTH

AF:

0.00808

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.0166

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 12, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.4

DANN

Benign

0.67

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over