rs1443435

Variant names:

• chr9-97855301-T-C
• rs1443435
• NM_004473.4:c.*265T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-97855301-T-C
• chr9-97855301-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.*265T>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 0.63 in 591,764 control chromosomes in the GnomAD database, including 119,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30788 hom., cov: 32)
  • Exomes 𝑓: 0.63 (88443 hom.)
• Consequence: FOXE1 NM_004473.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.372
• Publications: 14 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, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-97855301-T-C is Benign according to our data. Variant chr9-97855301-T-C is described in ClinVar as Benign. ClinVar VariationId is 1260357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 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.*265T>C		3_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.*265T>C		3_prime_UTR	Exon 1 of 1	ENSP00000364265.3

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96238 AN: 151898 Hom.: 30761 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.629 AC: 276465 AN: 439748 Hom.: 88443 Cov.: 3 AF XY: 0.626 AC XY: 143890 AN XY: 229934

African (AFR) AF: 0.652 AC: 7904 AN: 12120

American (AMR) AF: 0.664 AC: 12747 AN: 19200

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 6446 AN: 13292

East Asian (EAS) AF: 0.878 AC: 25470 AN: 29022

South Asian (SAS) AF: 0.617 AC: 28057 AN: 45488

European-Finnish (FIN) AF: 0.632 AC: 26218 AN: 41464

Middle Eastern (MID) AF: 0.531 AC: 988 AN: 1860

European-Non Finnish (NFE) AF: 0.607 AC: 153195 AN: 252550

Other (OTH) AF: 0.624 AC: 15440 AN: 24752

GnomAD4 genome AF: 0.633 AC: 96302 AN: 152016 Hom.: 30788 Cov.: 32 AF XY: 0.638 AC XY: 47392 AN XY: 74294

African (AFR) AF: 0.663 AC: 27490 AN: 41482

American (AMR) AF: 0.651 AC: 9955 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3466

East Asian (EAS) AF: 0.887 AC: 4554 AN: 5136

South Asian (SAS) AF: 0.632 AC: 3052 AN: 4826

European-Finnish (FIN) AF: 0.639 AC: 6759 AN: 10572

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40960 AN: 67940

Other (OTH) AF: 0.628 AC: 1326 AN: 2112

Alfa AF: 0.614 Hom.: 72801

Bravo AF: 0.637

Asia WGS AF: 0.720 AC: 2506 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.88
CADD	Benign	7.4
DANN	Benign	0.59
PhyloP100		0.37
Mutation Taster		=100/0	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: rs1443435; hg19: chr9-100617583; COSMIC: COSV64300103;