Genetic Variant FOXD1:p.Pro266Pro (chr5-73447565-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_004472.3(FOXD1):c.798G>A(p.Pro266Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,005,044 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000041 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

FOXD1
NM_004472.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0570

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 5-73447565-C-T is Benign according to our data. Variant chr5-73447565-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3056830.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.057 with no splicing effect.

BS2

High AC in GnomAd4 at 5 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.798G>A	p.Pro266Pro	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.798G>A	p.Pro266Pro	synonymous	Exon 1 of 1	ENSP00000481581.1	Q16676

Frequencies

GnomAD3 genomes

AF:

0.0000407

AC:

AN:

122714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000301

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:

0.0000696

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000793

AC:

AN:

882330

Hom.:

Cov.:

AF XY:

0.0000120

AC XY:

AN XY:

416184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16810

American (AMR)

AF:

0.00

AC:

AN:

3560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7118

East Asian (EAS)

AF:

0.00

AC:

AN:

7790

South Asian (SAS)

AF:

0.00

AC:

AN:

16896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1956

European-Non Finnish (NFE)

AF:

0.00000898

AC:

AN:

779524

Other (OTH)

AF:

0.00

AC:

AN:

30932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000407

AC:

AN:

122714

Hom.:

Cov.:

AF XY:

0.0000338

AC XY:

AN XY:

59206

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33238

American (AMR)

AF:

0.00

AC:

AN:

12214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2982

East Asian (EAS)

AF:

0.00

AC:

AN:

4094

South Asian (SAS)

AF:

0.00

AC:

AN:

3644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0000696

AC:

AN:

57436

Other (OTH)

AF:

0.00

AC:

AN:

1698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

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

Alfa

AF:

0.000214

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

FOXD1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

0.057

Mutation Taster

=100/0

polymorphism

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over