rs11669442

Variant names:

• chr19-45871299-T-C
• rs11669442
• NM_004497.3:c.70-776T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FOXA3	NM_004497.3	c.70-776T>C		intron_variant	Intron 1 of 1	ENST00000302177.3	NP_004488.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXA3	ENST00000302177.3	c.70-776T>C		intron_variant	Intron 1 of 1	1	NM_004497.3	ENSP00000304004.1
FOXA3	ENST00000594297.1	c.-30-776T>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.360 AC: 14915 AN: 41414

American (AMR) AF: 0.301 AC: 4591 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1508 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1527 AN: 5166

South Asian (SAS) AF: 0.287 AC: 1382 AN: 4822

European-Finnish (FIN) AF: 0.204 AC: 2151 AN: 10546

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22349 AN: 67968

Other (OTH) AF: 0.322 AC: 678 AN: 2108

Alfa AF: 0.330 Hom.: 35712

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
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11669442; hg19: chr19-46374557;