1-63322631-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_012183.3(FOXD3):c.-428C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 954,794 control chromosomes in the GnomAD database, including 4 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 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (4 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS2: High AC in GnomAd at 176 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 176 AN: 152060 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00244 AC: 1959 AN: 802620 Hom.: 4 AF XY: 0.00244 AC XY: 907 AN XY: 371384

Gnomad4 AFR exome AF: 0.000397

Gnomad4 AMR exome AF: 0.00106

Gnomad4 ASJ exome AF: 0.000202

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000630

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00259

Gnomad4 OTH exome AF: 0.00175

GnomAD4 genome AF: 0.00116 AC: 176 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.00116 AC XY: 86 AN XY: 74390

Gnomad4 AFR AF: 0.000554

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00191

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000173 Hom.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.6
Dann	Benign	0.63

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;