Variant 19-45872350-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_004497.3(FOXA3):c.345C>T(p.His115His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,614,180 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0069 ( 3 hom., cov: 32)

Exomes 𝑓: 0.010 ( 110 hom. )

Consequence

FOXA3
NM_004497.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.71

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=-0.52).

BP6

Variant 19-45872350-C-T is Benign according to our data. Variant chr19-45872350-C-T is described in ClinVar as [Benign]. Clinvar id is 3041583.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.71 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0103 (15111/1461844) while in subpopulation MID AF= 0.0182 (105/5768). AF 95% confidence interval is 0.0154. There are 110 homozygotes in gnomad4_exome. There are 7409 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1045 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXA3	NM_004497.3 linkuse as main transcript	c.345C>T	p.His115His	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.345C>T	p.His115His	synonymous_variant	2/2	1	NM_004497.3	ENSP00000304004.1		P55318
FOXA3	ENST00000594297.1 linkuse as main transcript	c.246C>T	p.His82His	synonymous_variant	2/2	3		ENSP00000470816.1		M0QZW5

Frequencies

GnomAD3 genomes

AF:

0.00685

AC:

1042

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00582

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00932

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00795

AC:

1996

AN:

251134

Hom.:

AF XY:

0.00820

AC XY:

1114

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00654

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00513

Gnomad FIN exome

AF:

0.00893

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.00847

GnomAD4 exome

AF:

0.0103

AC:

15111

AN:

1461844

Hom.:

110

Cov.:

AF XY:

0.0102

AC XY:

7409

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00662

Gnomad4 ASJ exome

AF:

0.00276

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00620

Gnomad4 FIN exome

AF:

0.00861

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.00886

GnomAD4 genome

AF:

0.00686

AC:

1045

AN:

152336

Hom.:

Cov.:

AF XY:

0.00663

AC XY:

494

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00581

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.00932

Gnomad4 NFE

AF:

0.0104

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00884

Hom.:

Bravo

AF:

0.00658

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0113

EpiControl

AF:

0.0100

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

May 15, 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

-0.52

CADD

Benign

2.4

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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