1-47416245-C-G

Position:

• chr1-47416245-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NR_126355.1(LINC01389):​n.29-6344G>C variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.344

Genes affected

LINC01389 (HGNC:):

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]

ACMG classification

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/exons	MANE	UniProt
LINC01389	NR_126355.1	n.29-6344G>C		intron_variant, non_coding_transcript_variant
FOXE3	NM_012186.3			upstream_gene_variant		ENST00000335071.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXE3	ENST00000335071.4			upstream_gene_variant			NM_012186.3	P1

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2218 AN: 151372 Hom.: 63 Cov.: 32

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.: 15 Cov.: 13 AF XY: 0.00122 AC XY: 548 AN XY: 448836

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.: 63 Cov.: 32 AF XY: 0.0137 AC XY: 1014 AN XY: 74042

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.: 2

Bravo AF: 0.0166

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2019	- -

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

Other links and lift over

dbSNP: rs551340839; hg19: chr1-47881917;