rs1867279

Variant names:

• chr9-97853759-T-C
• rs1867279
• NM_004473.4:c.-156T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-97853759-T-C
• chr9-97853759-T-G

Variant summary

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

The NM_004473.4(FOXE1):​c.-156T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 586,664 control chromosomes in the GnomAD database, including 178,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51344 hom., cov: 33)
  • Exomes 𝑓: 0.76 (127638 hom.)
• Consequence: FOXE1 NM_004473.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.375
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• Bamforth-Lazarus syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-97853759-T-C is Benign according to our data. Variant chr9-97853759-T-C is described in ClinVar as Benign. ClinVar VariationId is 1221326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004473.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXE1	NM_004473.4	MANE Select	c.-156T>C		5_prime_UTR	Exon 1 of 1	NP_004464.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXE1	ENST00000375123.5	TSL:6 MANE Select	c.-156T>C		5_prime_UTR	Exon 1 of 1	ENSP00000364265.3	O00358

Frequencies

GnomAD3 genomes AF: 0.816 AC: 123968 AN: 151984 Hom.: 51289 Cov.: 33

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.812

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.818

GnomAD4 exome AF: 0.763 AC: 331482 AN: 434568 Hom.: 127638 Cov.: 6 AF XY: 0.761 AC XY: 163007 AN XY: 214132

African (AFR) AF: 0.948 AC: 9528 AN: 10050

American (AMR) AF: 0.829 AC: 5469 AN: 6600

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 6740 AN: 8864

East Asian (EAS) AF: 0.996 AC: 20688 AN: 20774

South Asian (SAS) AF: 0.796 AC: 5335 AN: 6702

European-Finnish (FIN) AF: 0.807 AC: 16430 AN: 20354

Middle Eastern (MID) AF: 0.762 AC: 1205 AN: 1582

European-Non Finnish (NFE) AF: 0.737 AC: 249559 AN: 338512

Other (OTH) AF: 0.782 AC: 16528 AN: 21130

GnomAD4 genome AF: 0.816 AC: 124073 AN: 152096 Hom.: 51344 Cov.: 33 AF XY: 0.823 AC XY: 61184 AN XY: 74370

African (AFR) AF: 0.940 AC: 39063 AN: 41544

American (AMR) AF: 0.820 AC: 12544 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2643 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5104 AN: 5136

South Asian (SAS) AF: 0.800 AC: 3862 AN: 4828

European-Finnish (FIN) AF: 0.830 AC: 8794 AN: 10590

Middle Eastern (MID) AF: 0.818 AC: 239 AN: 292

European-Non Finnish (NFE) AF: 0.730 AC: 49564 AN: 67920

Other (OTH) AF: 0.821 AC: 1733 AN: 2112

Alfa AF: 0.692 Hom.: 2252

Bravo AF: 0.824

Asia WGS AF: 0.916 AC: 3178 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.7
DANN	Benign	0.36
PhyloP100		0.38
Mutation Taster		=298/2	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: rs1867279; hg19: chr9-100616041;