9-116869-C-T

Variant names:

• chr9-116869-C-T
• rs1819372385
• NM_207305.5:c.1251G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_207305.5(FOXD4):​c.1251G>A​(p.Glu417Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,638 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FOXD4 NM_207305.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 0 publications found

Genes affected

FOXD4 (HGNC:3805): (forkhead box D4) This gene encodes a member of the forkhead/winged helix-box (FOX) family of transcription factors. FOX transcription factors play critical roles in the regulation of multiple processes including metabolism, cell proliferation and gene expression during ontogenesis. Mutations in this gene are associated with a complex phenotype consisting of dilated cardiomyopathy, obsessive-compulsive disorders, and suicidality. [provided by RefSeq, Mar 2012]

ENSG00000302830 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-0.916 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207305.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXD4	NM_207305.5	MANE Select	c.1251G>A	p.Glu417Glu	synonymous	Exon 1 of 1	NP_997188.2	Q12950

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXD4	ENST00000382500.4	TSL:6 MANE Select	c.1251G>A	p.Glu417Glu	synonymous	Exon 1 of 1	ENSP00000371940.2	Q12950
	ENSG00000302830	ENST00000789896.1		n.699+1467C>T		intron	N/A
	ENSG00000302830	ENST00000789897.1		n.687+1467C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457638 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 724820

African (AFR) AF: 0.00 AC: 0 AN: 33298

American (AMR) AF: 0.00 AC: 0 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110608

Other (OTH) AF: 0.00 AC: 0 AN: 60076

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.0
DANN	Benign	0.93
PhyloP100		-0.92

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: rs1819372385; hg19: chr9-116869;