Genetic Variant NM_004472.3:c.789G>A (chr5-73447574-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_004472.3(FOXD1):c.789G>A(p.Pro263Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,032,064 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. Synonymous variant affecting the same amino acid position (i.e. P263P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000081 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

FOXD1
NM_004472.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.562

Publications

0 publications found

Variant links:

Genes affected

FOXD1 (HGNC:3802): (forkhead box D1) This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. Studies of the orthologous mouse protein indicate that it functions in kidney development by promoting nephron progenitor differentiation, and it also functions in the development of the retina and optic chiasm. It may also regulate inflammatory reactions and prevent autoimmunity. [provided by RefSeq, Apr 2014]

FOXD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=0.562 with no splicing effect.

BS2

High AC in GnomAdExome4 at 24 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004472.3. 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
	FOXD1	NM_004472.3	MANE Select	c.789G>A	p.Pro263Pro	synonymous	Exon 1 of 1	NP_004463.1	Q16676

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXD1	ENST00000615637.3	TSL:6 MANE Select	c.789G>A	p.Pro263Pro	synonymous	Exon 1 of 1	ENSP00000481581.1	Q16676

Frequencies

GnomAD3 genomes

AF:

0.00000808

AC:

AN:

123738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000175

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000264

AC:

AN:

908326

Hom.:

Cov.:

AF XY:

0.0000350

AC XY:

AN XY:

428606

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17382

American (AMR)

AF:

0.00

AC:

AN:

4022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7868

East Asian (EAS)

AF:

0.00

AC:

AN:

9672

South Asian (SAS)

AF:

0.00

AC:

AN:

17232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2052

European-Non Finnish (NFE)

AF:

0.0000226

AC:

AN:

796858

Other (OTH)

AF:

0.000187

AC:

AN:

32170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000808

AC:

AN:

123738

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

60034

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33554

American (AMR)

AF:

0.00

AC:

AN:

12510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2952

East Asian (EAS)

AF:

0.00

AC:

AN:

4092

South Asian (SAS)

AF:

0.00

AC:

AN:

3608

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000175

AC:

AN:

57244

Other (OTH)

AF:

0.00

AC:

AN:

1722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.56

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over