1-47416302-G-A

Variant names:

• chr1-47416302-G-A
• rs181190356
• NM_012186.3:c.-14G>A

Variant summary

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

The NM_012186.3(FOXE3):​c.-14G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 1,320,086 control chromosomes in the GnomAD database, including 1,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (250 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1411 hom.)
• Consequence: FOXE3 NM_012186.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.356
• Publications: 3 publications found

Genes affected

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]

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-47416302-G-A is Benign according to our data. Variant chr1-47416302-G-A is described in ClinVar as Benign. ClinVar VariationId is 260210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012186.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXE3	NM_012186.3	MANE Select	c.-14G>A		5_prime_UTR	Exon 1 of 1	NP_036318.1
	LINC01389	NR_126355.1		n.29-6401C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXE3	ENST00000335071.4	TSL:6 MANE Select	c.-14G>A		5_prime_UTR	Exon 1 of 1	ENSP00000334472.2
	LINC01389	ENST00000828805.1		n.207+17061C>T		intron	N/A
	LINC01389	ENST00000828806.1		n.92+929C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6499 AN: 150946 Hom.: 249 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.0266

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.0545

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0376

GnomAD2 exomes AF: 0.0812 AC: 2894 AN: 35650 AF XY: 0.0845

Gnomad AFR exome AF: 0.0177

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.0297

Gnomad EAS exome AF: 0.248

Gnomad FIN exome AF: 0.0566

Gnomad NFE exome AF: 0.0335

Gnomad OTH exome AF: 0.0600

GnomAD4 exome AF: 0.0352 AC: 41110 AN: 1169036 Hom.: 1411 Cov.: 30 AF XY: 0.0367 AC XY: 20859 AN XY: 568874

African (AFR) AF: 0.0227 AC: 550 AN: 24274

American (AMR) AF: 0.109 AC: 1855 AN: 16974

Ashkenazi Jewish (ASJ) AF: 0.0264 AC: 455 AN: 17236

East Asian (EAS) AF: 0.156 AC: 4064 AN: 26040

South Asian (SAS) AF: 0.128 AC: 5890 AN: 45924

European-Finnish (FIN) AF: 0.0489 AC: 1224 AN: 25046

Middle Eastern (MID) AF: 0.0671 AC: 217 AN: 3232

European-Non Finnish (NFE) AF: 0.0255 AC: 24530 AN: 963552

Other (OTH) AF: 0.0497 AC: 2325 AN: 46758

GnomAD4 genome AF: 0.0431 AC: 6516 AN: 151050 Hom.: 250 Cov.: 32 AF XY: 0.0484 AC XY: 3571 AN XY: 73712

African (AFR) AF: 0.0244 AC: 1013 AN: 41436

American (AMR) AF: 0.0833 AC: 1269 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.0266 AC: 91 AN: 3418

East Asian (EAS) AF: 0.188 AC: 958 AN: 5094

South Asian (SAS) AF: 0.135 AC: 652 AN: 4816

European-Finnish (FIN) AF: 0.0562 AC: 592 AN: 10528

Middle Eastern (MID) AF: 0.0517 AC: 15 AN: 290

European-Non Finnish (NFE) AF: 0.0272 AC: 1830 AN: 67228

Other (OTH) AF: 0.0429 AC: 90 AN: 2096

Alfa AF: 0.00567 Hom.: 1

Bravo AF: 0.0425

Asia WGS AF: 0.185 AC: 631 AN: 3418

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		0.36
PromoterAI		0.25	Neutral
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: rs181190356; hg19: chr1-47881974;