rs1055080

chr20-22581800-G-Achr20-22581800-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021784.5(FOXA2):c.*50C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 1,571,958 control chromosomes in the GnomAD database, including 17,559 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (8158 hom., cov: 32)
  • Exomes 𝑓: 0.064 (9401 hom.)
• Consequence: FOXA2 NM_021784.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXA2	NM_021784.5	c.*50C>T		3_prime_UTR_variant	2/2	ENST00000419308.7
FOXA2	NM_153675.3	c.*50C>T		3_prime_UTR_variant	3/3
FOXA2	XM_047440133.1	c.*50C>T		3_prime_UTR_variant	3/3
FOXA2	XM_047440134.1	c.*50C>T		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXA2	ENST00000419308.7	c.*50C>T		3_prime_UTR_variant	2/2	1	NM_021784.5	P4
FOXA2	ENST00000377115.4	c.*50C>T		3_prime_UTR_variant	3/3	1		A1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32113 AN: 151842 Hom.: 8107 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.176

GnomAD3 exomes AF: 0.101 AC: 24680 AN: 244094 Hom.: 3797 AF XY: 0.0931 AC XY: 12331 AN XY: 132498

Gnomad AFR exome AF: 0.631

Gnomad AMR exome AF: 0.0562

Gnomad ASJ exome AF: 0.0938

Gnomad EAS exome AF: 0.183

Gnomad SAS exome AF: 0.0998

Gnomad FIN exome AF: 0.0270

Gnomad NFE exome AF: 0.0444

Gnomad OTH exome AF: 0.0806

GnomAD4 exome AF: 0.0639 AC: 90668 AN: 1419998 Hom.: 9401 Cov.: 26 AF XY: 0.0635 AC XY: 44845 AN XY: 705892

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.0588

Gnomad4 ASJ exome AF: 0.0942

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.0992

Gnomad4 FIN exome AF: 0.0292

Gnomad4 NFE exome AF: 0.0382

Gnomad4 OTH exome AF: 0.0997

GnomAD4 genome AF: 0.212 AC: 32219 AN: 151960 Hom.: 8158 Cov.: 32 AF XY: 0.206 AC XY: 15312 AN XY: 74300

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.0918

Gnomad4 ASJ AF: 0.0980

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0250

Gnomad4 NFE AF: 0.0443

Gnomad4 OTH AF: 0.177

Alfa AF: 0.103 Hom.: 1552

Bravo AF: 0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.47
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs1055080; hg19: chr20-22562438;