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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD1	NM_004472.3 link	c.798G>A	p.Pro266Pro	synonymous_variant	Exon 1 of 1	ENST00000615637.3	NP_004463.1	Q16676

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD1	ENST00000615637.3 link	c.798G>A	p.Pro266Pro	synonymous_variant	Exon 1 of 1	6	NM_004472.3	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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000898

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000407

AC:

AN:

122714

Hom.:

Cov.:

AF XY:

0.0000338

AC XY:

AN XY:

59206

show subpopulations

Gnomad4 AFR

AF:

0.0000301

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000696

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FOXD1-related disorder

Benign:1

Jul 12, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.93

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over