Genetic Variant FOXD1:p.Gln383_Ala387del (chr5-73447202-GGCGGCGGCGGCCTGC-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM4BP6BA1

The NM_004472.3(FOXD1):c.1146_1160delGCAGGCCGCCGCCGC(p.Gln383_Ala387del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 992,676 control chromosomes in the GnomAD database, including 1,160 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.030 ( 96 hom., cov: 31)

Exomes 𝑓: 0.048 ( 1064 hom. )

Consequence

FOXD1
NM_004472.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.12

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:

FOXD1-AS1 (HGNC:50658): (FOXD1 antisense RNA 1)

FOXD1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_004472.3.

BP6

Variant 5-73447202-GGCGGCGGCGGCCTGC-G is Benign according to our data. Variant chr5-73447202-GGCGGCGGCGGCCTGC-G is described in ClinVar as [Benign]. Clinvar id is 3042166.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-73447202-GGCGGCGGCGGCCTGC-G is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.05 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD1	NM_004472.3 link	c.1146_1160delGCAGGCCGCCGCCGC	p.Gln383_Ala387del	disruptive_inframe_deletion	Exon 1 of 1	ENST00000615637.3	NP_004463.1	Q16676

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXD1	ENST00000615637.3 link	c.1146_1160delGCAGGCCGCCGCCGC	p.Gln383_Ala387del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_004472.3	ENSP00000481581.1	Q16676
FOXD1	ENST00000513595.1 link	n.-229_-215delGCAGGCCGCCGCCGC		upstream_gene_variant		3
FOXD1-AS1	ENST00000514661.1 link	n.219_233delGCGGCGGCGGCCTGC		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0296

AC:

4312

AN:

145828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00821

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.000987

Gnomad SAS

AF:

0.0262

Gnomad FIN

AF:

0.0291

Gnomad MID

AF:

0.00980

Gnomad NFE

AF:

0.0460

Gnomad OTH

AF:

0.0259

GnomAD3 exomes

AF:

0.0224

AC:

AN:

134

Hom.:

AF XY:

0.0385

AC XY:

AN XY:

show subpopulations

Gnomad FIN exome

AF:

0.0238

Gnomad NFE exome

AF:

0.0222

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0483

AC:

40919

AN:

846740

Hom.:

1064

AF XY:

0.0483

AC XY:

19033

AN XY:

393808

show subpopulations

Gnomad4 AFR exome

AF:

0.00443

Gnomad4 AMR exome

AF:

0.0394

Gnomad4 ASJ exome

AF:

0.0157

Gnomad4 EAS exome

AF:

0.000726

Gnomad4 SAS exome

AF:

0.0298

Gnomad4 FIN exome

AF:

0.0354

Gnomad4 NFE exome

AF:

0.0505

Gnomad4 OTH exome

AF:

0.0414

GnomAD4 genome

AF:

0.0295

AC:

4311

AN:

145936

Hom.:

Cov.:

AF XY:

0.0276

AC XY:

1963

AN XY:

71022

show subpopulations

Gnomad4 AFR

AF:

0.00818

Gnomad4 AMR

AF:

0.0263

Gnomad4 ASJ

AF:

0.0133

Gnomad4 EAS

AF:

0.000990

Gnomad4 SAS

AF:

0.0260

Gnomad4 FIN

AF:

0.0291

Gnomad4 NFE

AF:

0.0460

Gnomad4 OTH

AF:

0.0257

Bravo

AF:

0.0271

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FOXD1-related disorder

Benign:1

May 14, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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

Splicing

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