rs1800847

Variant names:

• chr20-22582933-G-A
• rs1800847
• NM_021784.5:c.309C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-22582933-G-A
• chr20-22582933-G-C
• chr20-22582933-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_021784.5(FOXA2):​c.309C>T​(p.Ala103Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 1,528,470 control chromosomes in the GnomAD database, including 3,153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (733 hom., cov: 33)
  • Exomes 𝑓: 0.047 (2420 hom.)
• Consequence: FOXA2 NM_021784.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.643
• Publications: 8 publications found

Genes affected

FOXA2 (HGNC:5022): (forkhead box A2) This gene encodes a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific genes 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. This gene has been linked to sporadic cases of maturity-onset diabetes of the young. Transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

FOXA2 Gene-Disease associations (from GenCC):

• combined pituitary hormone deficiencies, genetic form

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 20-22582933-G-A is Benign according to our data. Variant chr20-22582933-G-A is described in ClinVar as Benign. ClinVar VariationId is 1569424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.643 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXA2	NM_021784.5	c.309C>T	p.Ala103Ala	synonymous_variant	Exon 2 of 2	ENST00000419308.7	NP_068556.2
FOXA2	NM_153675.3	c.291C>T	p.Ala97Ala	synonymous_variant	Exon 3 of 3		NP_710141.1
FOXA2	XM_047440133.1	c.291C>T	p.Ala97Ala	synonymous_variant	Exon 3 of 3		XP_047296089.1
FOXA2	XM_047440134.1	c.201C>T	p.Ala67Ala	synonymous_variant	Exon 2 of 2		XP_047296090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXA2	ENST00000419308.7	c.309C>T	p.Ala103Ala	synonymous_variant	Exon 2 of 2	1	NM_021784.5	ENSP00000400341.3
FOXA2	ENST00000377115.4	c.291C>T	p.Ala97Ala	synonymous_variant	Exon 3 of 3	1		ENSP00000366319.4

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12133 AN: 151914 Hom.: 727 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0453

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.0233

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0401

Gnomad OTH AF: 0.0786

GnomAD2 exomes AF: 0.0712 AC: 9347 AN: 131320 AF XY: 0.0710

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.0342

Gnomad ASJ exome AF: 0.0989

Gnomad EAS exome AF: 0.180

Gnomad FIN exome AF: 0.0258

Gnomad NFE exome AF: 0.0468

Gnomad OTH exome AF: 0.0658

GnomAD4 exome AF: 0.0469 AC: 64568 AN: 1376450 Hom.: 2420 Cov.: 35 AF XY: 0.0481 AC XY: 32709 AN XY: 680274

African (AFR) AF: 0.174 AC: 5175 AN: 29662

American (AMR) AF: 0.0329 AC: 1069 AN: 32460

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 2136 AN: 23400

East Asian (EAS) AF: 0.183 AC: 6439 AN: 35214

South Asian (SAS) AF: 0.0838 AC: 6441 AN: 76902

European-Finnish (FIN) AF: 0.0274 AC: 1126 AN: 41020

Middle Eastern (MID) AF: 0.0604 AC: 302 AN: 4996

European-Non Finnish (NFE) AF: 0.0355 AC: 38234 AN: 1075730

Other (OTH) AF: 0.0639 AC: 3646 AN: 57066

GnomAD4 genome AF: 0.0800 AC: 12161 AN: 152020 Hom.: 733 Cov.: 33 AF XY: 0.0792 AC XY: 5888 AN XY: 74322

African (AFR) AF: 0.161 AC: 6663 AN: 41492

American (AMR) AF: 0.0452 AC: 690 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 315 AN: 3470

East Asian (EAS) AF: 0.157 AC: 807 AN: 5132

South Asian (SAS) AF: 0.0869 AC: 419 AN: 4822

European-Finnish (FIN) AF: 0.0233 AC: 246 AN: 10568

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.0401 AC: 2727 AN: 67942

Other (OTH) AF: 0.0802 AC: 169 AN: 2108

Alfa AF: 0.0361 Hom.: 53

Bravo AF: 0.0849

Asia WGS AF: 0.148 AC: 508 AN: 3452

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

FOXA2-related disorder Benign:1

Sep 17, 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	-0.62
CADD	Benign	5.1
DANN	Benign	0.94
PhyloP100		-0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800847; hg19: chr20-22563571;