rs1055080

Variant names:

• chr20-22581800-G-A
• rs1055080
• NM_021784.5:c.*50C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-22581800-G-A
• chr20-22581800-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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 -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 rank	MANE	Protein	UniProt
FOXA2	NM_021784.5	c.*50C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000419308.7	NP_068556.2
FOXA2	NM_153675.3	c.*50C>T		3_prime_UTR_variant	Exon 3 of 3		NP_710141.1
FOXA2	XM_047440133.1	c.*50C>T		3_prime_UTR_variant	Exon 3 of 3		XP_047296089.1
FOXA2	XM_047440134.1	c.*50C>T		3_prime_UTR_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.*50C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_021784.5	ENSP00000400341.3
FOXA2	ENST00000377115.4	c.*50C>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000366319.4

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

GnomAD2 exomes AF: 0.101 AC: 24680 AN: 244094 AF XY: 0.0931

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 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

African (AFR) AF: 0.632 AC: 20535 AN: 32488

American (AMR) AF: 0.0588 AC: 2579 AN: 43824

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 2386 AN: 25324

East Asian (EAS) AF: 0.196 AC: 7709 AN: 39256

South Asian (SAS) AF: 0.0992 AC: 8351 AN: 84156

European-Finnish (FIN) AF: 0.0292 AC: 1552 AN: 53152

Middle Eastern (MID) AF: 0.119 AC: 554 AN: 4636

European-Non Finnish (NFE) AF: 0.0382 AC: 41158 AN: 1078572

Other (OTH) AF: 0.0997 AC: 5844 AN: 58590

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

African (AFR) AF: 0.609 AC: 25197 AN: 41360

American (AMR) AF: 0.0918 AC: 1402 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3468

East Asian (EAS) AF: 0.188 AC: 966 AN: 5140

South Asian (SAS) AF: 0.106 AC: 510 AN: 4810

European-Finnish (FIN) AF: 0.0250 AC: 265 AN: 10602

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0443 AC: 3013 AN: 67988

Other (OTH) AF: 0.177 AC: 373 AN: 2110

Alfa AF: 0.164 Hom.: 4208

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
PhyloP100		-0.34
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: rs1055080; hg19: chr20-22562438;