rs7043516

Positions:

• chr9-97855151-A-C
• chr9-97855151-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19

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]

ACMG classification

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/exons	MANE	UniProt
FOXE1	NM_004473.4	c.*115A>C		3_prime_UTR_variant	1/1	ENST00000375123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXE1	ENST00000375123.5	c.*115A>C		3_prime_UTR_variant	1/1		NM_004473.4	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27148 AN: 152110 Hom.: 2785 Cov.: 34

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.: 17 AF XY: 0.135 AC XY: 79816 AN XY: 590638

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.: 34 AF XY: 0.180 AC XY: 13432 AN XY: 74428

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	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

Other links and lift over

dbSNP: rs7043516; hg19: chr9-100617433; COSMIC: COSV64300734;