Variant rs16980091 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.516C>T(p.Asn172Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,613,992 control chromosomes in the GnomAD database, including 16,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.17 ( 2700 hom., cov: 32)

Exomes 𝑓: 0.12 ( 13808 hom. )

Consequence

FOXA3
NM_004497.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.128

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=-0.53).

BP6

Variant 19-45872521-C-T is Benign according to our data. Variant chr19-45872521-C-T is described in ClinVar as [Benign]. Clinvar id is 3060822.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.128 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 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.516C>T	p.Asn172Asn	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.516C>T	p.Asn172Asn	synonymous_variant	2/2	1	NM_004497.3	ENSP00000304004.1		P55318

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25350

AN:

152060

Hom.:

2695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.374

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.166

GnomAD3 exomes

AF:

0.142

AC:

35634

AN:

251330

Hom.:

3534

AF XY:

0.141

AC XY:

19108

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.0737

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.372

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.120

AC:

175822

AN:

1461814

Hom.:

13808

Cov.:

AF XY:

0.121

AC XY:

88327

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.0790

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.426

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.100

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.167

AC:

25375

AN:

152178

Hom.:

2700

Cov.:

AF XY:

0.168

AC XY:

12535

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.374

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.164

Alfa

AF:

0.118

Hom.:

1744

Bravo

AF:

0.172

Asia WGS

AF:

0.235

AC:

817

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.100

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

Nov 06, 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

-0.53

CADD

Benign

4.6

DANN

Benign

0.88

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