dbSNP rs16980091: FOXA3:p.Asn172Asn (chr19-45872521-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

20 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
FOXA3	NM_004497.3 link	c.516C>T	p.Asn172Asn	synonymous_variant	Exon 2 of 2	ENST00000302177.3	NP_004488.2	P55318A0A024R0R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXA3	ENST00000302177.3 link	c.516C>T	p.Asn172Asn	synonymous_variant	Exon 2 of 2	1	NM_004497.3	ENSP00000304004.1		P55318
FOXA3	ENST00000594297.1 link	c.*112C>T		downstream_gene_variant		3		ENSP00000470816.1		M0QZW5

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

GnomAD2 exomes

AF:

0.142

AC:

35634

AN:

251330

AF XY:

0.141

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 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

African (AFR)

AF:

0.294

AC:

9840

AN:

33480

American (AMR)

AF:

0.0790

AC:

3532

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

3400

AN:

26136

East Asian (EAS)

AF:

0.426

AC:

16895

AN:

39698

South Asian (SAS)

AF:

0.172

AC:

14839

AN:

86258

European-Finnish (FIN)

AF:

0.125

AC:

6656

AN:

53358

Middle Eastern (MID)

AF:

0.138

AC:

794

AN:

5768

European-Non Finnish (NFE)

AF:

0.100

AC:

111515

AN:

1111998

Other (OTH)

AF:

0.138

AC:

8351

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

11665

23330

34994

46659

58324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4362

8724

13086

17448

21810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.167

AC:

25375

AN:

152178

Hom.:

2700

Cov.:

AF XY:

0.168

AC XY:

12535

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.279

AC:

11580

AN:

41506

American (AMR)

AF:

0.115

AC:

1751

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

479

AN:

3468

East Asian (EAS)

AF:

0.374

AC:

1930

AN:

5156

South Asian (SAS)

AF:

0.183

AC:

883

AN:

4824

European-Finnish (FIN)

AF:

0.121

AC:

1287

AN:

10610

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7075

AN:

68002

Other (OTH)

AF:

0.164

AC:

347

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1038

2076

3114

4152

5190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.119

Hom.:

2022

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

Nov 06, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.88

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over