dbSNP rs7043516: FOXE1:c.*115A>C (chr9-97855151-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004473.4(FOXE1):c.*115A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,330,334 control chromosomes in the GnomAD database, including 14,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2796 hom., cov: 34)

Exomes 𝑓: 0.13 ( 11870 hom. )

Consequence

FOXE1
NM_004473.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.19

Variant links:

Genes affected

FOXE1 (HGNC:3806): (forkhead box E1) This intronless gene encodes a protein that belongs to the forkhead family of transcription factors. Members of this family contain a conserved 100-amino acid DNA-binding 'forkhead' domain. The encoded protein functions as a thyroid transcription factor that plays a role in thyroid morphogenesis. Mutations in this gene are associated with the Bamforth-Lazarus syndrome, and with susceptibility to nonmedullary thyroid cancer-4. [provided by RefSeq, Nov 2016]

FOXE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 9-97855151-A-C is Benign according to our data. Variant chr9-97855151-A-C is described in ClinVar as [Benign]. Clinvar id is 1228293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXE1	NM_004473.4 link	c.*115A>C		3_prime_UTR_variant	Exon 1 of 1	ENST00000375123.5	NP_004464.2	O00358

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXE1	ENST00000375123.5 link	c.*115A>C		3_prime_UTR_variant	Exon 1 of 1	6	NM_004473.4	ENSP00000364265.3		O00358

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27148

AN:

152110

Hom.:

2785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.0435

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.187

GnomAD4 exome

AF:

0.135

AC:

159002

AN:

1178106

Hom.:

11870

Cov.:

AF XY:

0.135

AC XY:

79816

AN XY:

590638

show subpopulations

Gnomad4 AFR exome

AF:

0.281

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.0445

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.179

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.179

AC:

27196

AN:

152228

Hom.:

2796

Cov.:

AF XY:

0.180

AC XY:

13432

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.275

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.0436

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.137

Hom.:

1971

Bravo

AF:

0.183

Asia WGS

AF:

0.169

AC:

587

AN:

3478

ClinVar

Significance: 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: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26728781) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.0

DANN

Benign

0.39

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