dbSNP rs1369165182: FOXA1:p.Ser285Ile (chr14-37591930-C-A) – 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_004496.5(FOXA1):c.854G>T(p.Ser285Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000746 in 1,340,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S285N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

FOXA1
NM_004496.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.21

Publications

0 publications found

Variant links:

Genes affected

FOXA1 (HGNC:5021): (forkhead box A1) This gene encodes a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as albumin and transthyretin, and they also interact with chromatin. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver. [provided by RefSeq, Jul 2008]

FOXA1 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=0.23757046).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004496.5. 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
	FOXA1	NM_004496.5	MANE Select	c.854G>T	p.Ser285Ile	missense	Exon 2 of 2	NP_004487.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXA1	ENST00000250448.5	TSL:1 MANE Select	c.854G>T	p.Ser285Ile	missense	Exon 2 of 2	ENSP00000250448.3	P55317-1
	FOXA1	ENST00000545425.2	TSL:2	n.969G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.46e-7

AC:

AN:

1340794

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

657148

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29432

American (AMR)

AF:

0.00

AC:

AN:

27602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20404

East Asian (EAS)

AF:

0.00

AC:

AN:

35752

South Asian (SAS)

AF:

0.00

AC:

AN:

68892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41860

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4172

European-Non Finnish (NFE)

AF:

9.46e-7

AC:

AN:

1057380

Other (OTH)

AF:

0.00

AC:

AN:

55300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Uncertain

0.46

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.26

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.46

MutationAssessor

Benign

0.69

PhyloP100

1.2

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.1

REVEL

Benign

0.13

Sift

Benign

0.081

Sift4G

Benign

0.14

Polyphen

0.077

Vest4

0.16

MutPred

0.31

Gain of catalytic residue at S280 (P = 0)

MVP

0.57

ClinPred

0.11

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.16

gMVP

0.36

Mutation Taster

=94/6

polymorphism

(source)

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

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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