chr9-97855197-G-T

Variant names:

• chr9-97855197-G-T
• rs1443434
• NM_004473.4:c.*161G>T

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.*161G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 887,464 control chromosomes in the GnomAD database, including 173,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30776 hom., cov: 33)
  • Exomes 𝑓: 0.62 (142500 hom.)
• Consequence: FOXE1 NM_004473.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.669
• Publications: 29 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=-0.82).
• BP6: Variant 9-97855197-G-T is Benign according to our data. Variant chr9-97855197-G-T is described in ClinVar as Benign. ClinVar VariationId is 1247020.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXE1	NM_004473.4	c.*161G>T		3_prime_UTR_variant	Exon 1 of 1	ENST00000375123.5	NP_004464.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXE1	ENST00000375123.5	c.*161G>T		3_prime_UTR_variant	Exon 1 of 1	6	NM_004473.4	ENSP00000364265.3

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96228 AN: 151936 Hom.: 30749 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.617 AC: 454012 AN: 735410 Hom.: 142500 Cov.: 10 AF XY: 0.616 AC XY: 235885 AN XY: 383050

African (AFR) AF: 0.657 AC: 12372 AN: 18822

American (AMR) AF: 0.675 AC: 23147 AN: 34290

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 9682 AN: 19974

East Asian (EAS) AF: 0.877 AC: 28653 AN: 32656

South Asian (SAS) AF: 0.616 AC: 39085 AN: 63448

European-Finnish (FIN) AF: 0.634 AC: 30032 AN: 47380

Middle Eastern (MID) AF: 0.533 AC: 1470 AN: 2758

European-Non Finnish (NFE) AF: 0.598 AC: 287339 AN: 480122

Other (OTH) AF: 0.618 AC: 22232 AN: 35960

GnomAD4 genome AF: 0.633 AC: 96292 AN: 152054 Hom.: 30776 Cov.: 33 AF XY: 0.638 AC XY: 47407 AN XY: 74334

African (AFR) AF: 0.662 AC: 27488 AN: 41498

American (AMR) AF: 0.652 AC: 9954 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3472

East Asian (EAS) AF: 0.886 AC: 4569 AN: 5154

South Asian (SAS) AF: 0.632 AC: 3049 AN: 4822

European-Finnish (FIN) AF: 0.640 AC: 6779 AN: 10590

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40927 AN: 67936

Other (OTH) AF: 0.628 AC: 1323 AN: 2106

Alfa AF: 0.621 Hom.: 28319

Bravo AF: 0.637

Asia WGS AF: 0.720 AC: 2507 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.54
PhyloP100		-0.67
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: rs1443434; hg19: chr9-100617479; COSMIC: COSV64300097;