rs11669442

Positions:

• chr19-45871299-T-C

Variant summary

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

The NM_004497.3(FOXA3):​c.70-776T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,948 control chromosomes in the GnomAD database, including 8,262 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 0.33 (8262 hom., cov: 31)
• Consequence: FOXA3 NM_004497.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXA3	NM_004497.3	c.70-776T>C		intron_variant		ENST00000302177.3	NP_004488.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXA3	ENST00000302177.3	c.70-776T>C		intron_variant		1	NM_004497.3	ENSP00000304004.1
FOXA3	ENST00000594297.1	c.-30-776T>C		intron_variant		3		ENSP00000470816.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49557 AN: 151830 Hom.: 8250 Cov.: 31

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.325

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.326 AC: 49609 AN: 151948 Hom.: 8262 Cov.: 31 AF XY: 0.318 AC XY: 23637 AN XY: 74280

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.322

Alfa AF: 0.332 Hom.: 17436

Bravo AF: 0.335

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11669442; hg19: chr19-46374557;