rs7043516

Variant names:

• chr9-97855151-A-C
• rs7043516
• NM_004473.4:c.*115A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-97855151-A-C
• chr9-97855151-A-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.*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
• Publications: 12 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: Laboratory for Molecular Medicine, G2P, Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-97855151-A-C is Benign according to our data. Variant chr9-97855151-A-C is described in ClinVar as Benign. ClinVar VariationId 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.

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.*115A>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.*115A>C		3_prime_UTR	Exon 1 of 1	ENSP00000364265.3	O00358

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

African (AFR) AF: 0.281 AC: 7650 AN: 27232

American (AMR) AF: 0.168 AC: 5985 AN: 35638

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 6571 AN: 23808

East Asian (EAS) AF: 0.0445 AC: 1549 AN: 34824

South Asian (SAS) AF: 0.148 AC: 11087 AN: 74876

European-Finnish (FIN) AF: 0.179 AC: 8642 AN: 48374

Middle Eastern (MID) AF: 0.222 AC: 852 AN: 3830

European-Non Finnish (NFE) AF: 0.124 AC: 108854 AN: 878806

Other (OTH) AF: 0.154 AC: 7812 AN: 50718

GnomAD4 genome AF: 0.179 AC: 27196 AN: 152228 Hom.: 2796 Cov.: 34 AF XY: 0.180 AC XY: 13432 AN XY: 74428

African (AFR) AF: 0.275 AC: 11416 AN: 41510

American (AMR) AF: 0.167 AC: 2552 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3468

East Asian (EAS) AF: 0.0436 AC: 226 AN: 5182

South Asian (SAS) AF: 0.154 AC: 743 AN: 4828

European-Finnish (FIN) AF: 0.190 AC: 2018 AN: 10594

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8640 AN: 68024

Other (OTH) AF: 0.190 AC: 401 AN: 2114

Alfa AF: 0.144 Hom.: 6209

Bravo AF: 0.183

Asia WGS AF: 0.169 AC: 587 AN: 3478

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	-0.82
CADD	Benign	4.0
DANN	Benign	0.39
PhyloP100		-1.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7043516;

hg19: chr9-100617433;

COSMIC: COSV64300734;