5-73447565-C-T

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

2

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]

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
FOXD1NM_004472.3 linkc.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
FOXD1ENST00000615637.3 linkc.798G>A p.Pro266Pro synonymous_variant Exon 1 of 1 6 NM_004472.3 ENSP00000481581.1 Q16676

Frequencies

GnomAD3 genomes
AF:
0.0000407
AC:
5
AN:
122714
Hom.:
1
Cov.:
31
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:
7
AN:
882330
Hom.:
0
Cov.:
32
AF XY:
0.0000120
AC XY:
5
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:
5
AN:
122714
Hom.:
1
Cov.:
31
AF XY:
0.0000338
AC XY:
2
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.:
0

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
11
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.

Other links and lift over

dbSNP: rs1177349530; hg19: chr5-72743390; API