Genetic Variant FOXB1:p.Asp115Glu (chr15-60005308-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012182.3(FOXB1):c.345C>G(p.Asp115Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

FOXB1
NM_012182.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.103

Publications

0 publications found

Variant links:

Genes affected

FOXB1 (HGNC:3799): (forkhead box B1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including mammary gland development; nervous system development; and visual learning. Predicted to act upstream of or within spinal cord development; thalamus development; and urogenital system development. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

FOXB1 links:

ENSG00000289162 (HGNC:):

ENSG00000289162 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07399216).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012182.3. 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
	FOXB1	NM_012182.3	MANE Select	c.345C>G	p.Asp115Glu	missense	Exon 2 of 2	NP_036314.2	Q99853

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXB1	ENST00000396057.6	TSL:1 MANE Select	c.345C>G	p.Asp115Glu	missense	Exon 2 of 2	ENSP00000379369.4	Q99853
ENSG00000289162	ENST00000824570.1		n.121G>C		non_coding_transcript_exon	Exon 1 of 2
FOXB1	ENST00000560857.1	TSL:3	n.410+665C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152218

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.16

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.72

M_CAP

Benign

0.036

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.41

MutationAssessor

Benign

0.53

PhyloP100

0.10

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.44

REVEL

Uncertain

0.33

Sift

Benign

0.72

Sift4G

Benign

0.48

Polyphen

0.0010

Vest4

0.029

MutPred

0.20

Loss of MoRF binding (P = 0.1216)

MVP

0.51

MPC

0.79

ClinPred

0.11

GERP RS

1.8

Varity_R

0.061

gMVP

0.65

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over