1-63322631-C-T

Variant summary

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

The NM_012183.3(FOXD3):c.-428C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 954,416 control chromosomes in the GnomAD database, including 3,524 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 0.062 (374 hom., cov: 33)
  • Exomes 𝑓: 0.088 (3150 hom.)
• Consequence: FOXD3 NM_012183.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

Genes affected

FOXD3 (HGNC:3804): (forkhead box D3) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. Mutations in this gene cause autoimmune susceptibility 1. [provided by RefSeq, Nov 2008]

FOXD3-AS1 (HGNC:40241): (FOXD3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXD3	NM_012183.3	c.-428C>T		5_prime_UTR_variant	1/1	ENST00000371116.4
FOXD3-AS1	NR_121637.1	n.88-1168G>A		intron_variant, non_coding_transcript_variant
FOXD3-AS1	NR_121636.1	n.185+860G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXD3	ENST00000371116.4	c.-428C>T		5_prime_UTR_variant	1/1		NM_012183.3	P1
FOXD3-AS1	ENST00000427268.1	n.88-1168G>A		intron_variant, non_coding_transcript_variant		1
FOXD3-AS1	ENST00000431294.7	n.286+860G>A		intron_variant, non_coding_transcript_variant		1
FOXD3-AS1	ENST00000697579.1	n.368G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9369 AN: 152050 Hom.: 374 Cov.: 33

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0518

Gnomad AMR AF: 0.0653

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.0201

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0831

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.0670

GnomAD4 exome AF: 0.0877 AC: 70336 AN: 802252 Hom.: 3150 AF XY: 0.0875 AC XY: 32464 AN XY: 371222

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.0594

Gnomad4 ASJ exome AF: 0.0851

Gnomad4 EAS exome AF: 0.0237

Gnomad4 SAS exome AF: 0.0249

Gnomad4 FIN exome AF: 0.0778

Gnomad4 NFE exome AF: 0.0914

Gnomad4 OTH exome AF: 0.0763

GnomAD4 genome AF: 0.0616 AC: 9369 AN: 152164 Hom.: 374 Cov.: 33 AF XY: 0.0595 AC XY: 4424 AN XY: 74386

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.0652

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.0200

Gnomad4 SAS AF: 0.0261

Gnomad4 FIN AF: 0.0831

Gnomad4 NFE AF: 0.0877

Gnomad4 OTH AF: 0.0668

Alfa AF: 0.0330 Hom.: 26

Bravo AF: 0.0588

Asia WGS AF: 0.0380 AC: 131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	9.1
Dann	Benign	0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs78645479; hg19: chr1-63788302;