Variant rs3810327 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004497.3(FOXA3):c.954C>A(p.Pro318Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.091 in 1,613,926 control chromosomes in the GnomAD database, including 7,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.080 ( 545 hom., cov: 32)

Exomes 𝑓: 0.092 ( 6678 hom. )

Consequence

FOXA3
NM_004497.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

FOXA3 (HGNC:5023): (forkhead box A3) 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. The crystal structure of a similar protein in rat has been resolved. [provided by RefSeq, Jul 2008]

FOXA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 19-45872959-C-A is Benign according to our data. Variant chr19-45872959-C-A is described in ClinVar as [Benign]. Clinvar id is 3059205.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXA3	NM_004497.3 linkuse as main transcript	c.954C>A	p.Pro318Pro	synonymous_variant	2/2	ENST00000302177.3	NP_004488.2	P55318A0A024R0R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXA3	ENST00000302177.3 linkuse as main transcript	c.954C>A	p.Pro318Pro	synonymous_variant	2/2	1	NM_004497.3	ENSP00000304004.1		P55318

Frequencies

GnomAD3 genomes

AF:

0.0798

AC:

12126

AN:

152014

Hom.:

546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0338

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0601

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.0657

Gnomad SAS

AF:

0.0972

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0992

Gnomad OTH

AF:

0.0853

GnomAD3 exomes

AF:

0.0898

AC:

22544

AN:

251014

Hom.:

1154

AF XY:

0.0932

AC XY:

12661

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0299

Gnomad AMR exome

AF:

0.0498

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.0561

Gnomad SAS exome

AF:

0.0974

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.0922

AC:

134813

AN:

1461794

Hom.:

6678

Cov.:

AF XY:

0.0929

AC XY:

67542

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0314

Gnomad4 AMR exome

AF:

0.0521

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.0834

Gnomad4 SAS exome

AF:

0.0958

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.0927

Gnomad4 OTH exome

AF:

0.0885

GnomAD4 genome

AF:

0.0797

AC:

12127

AN:

152132

Hom.:

545

Cov.:

AF XY:

0.0824

AC XY:

6130

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0337

Gnomad4 AMR

AF:

0.0599

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.0659

Gnomad4 SAS

AF:

0.0970

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.0992

Gnomad4 OTH

AF:

0.0873

Alfa

AF:

0.0899

Hom.:

501

Bravo

AF:

0.0694

Asia WGS

AF:

0.0890

AC:

310

AN:

3478

EpiCase

AF:

0.0908

EpiControl

AF:

0.0933

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FOXA3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.8

DANN

Benign

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over