Genetic Variant FOXD1:p.Ala387_Ala388insGlnAlaAlaAlaAla (chr5-73447202-G-GGCGGCGGCGGCCTGC) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM4BS2

The NM_004472.3(FOXD1):c.1146_1160dupGCAGGCCGCCGCCGC(p.Ala387_Ala388insGlnAlaAlaAlaAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 992,660 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

FOXD1
NM_004472.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.257

Publications

1 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:

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

FOXD1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_004472.3.

BS2

High AC in GnomAd4 at 10 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.1146_1160dupGCAGGCCGCCGCCGC	p.Ala387_Ala388insGlnAlaAlaAlaAla	disruptive_inframe_insertion	Exon 1 of 1	NP_004463.1	Q16676

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXD1	ENST00000615637.3	TSL:6 MANE Select	c.1146_1160dupGCAGGCCGCCGCCGC	p.Ala387_Ala388insGlnAlaAlaAlaAla	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000481581.1	Q16676
FOXD1	ENST00000513595.1	TSL:3	n.-229_-215dupGCAGGCCGCCGCCGC		upstream_gene	N/A
FOXD1-AS1	ENST00000514661.1	TSL:3	n.218_219insGCGGCGGCGGCCTGC		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000686

AC:

AN:

145856

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:

0.000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000125

AC:

106

AN:

846804

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

393836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15794

American (AMR)

AF:

0.000743

AC:

AN:

1346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5342

East Asian (EAS)

AF:

0.00

AC:

AN:

4132

South Asian (SAS)

AF:

0.00

AC:

AN:

17442

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1670

European-Non Finnish (NFE)

AF:

0.000131

AC:

101

AN:

771942

Other (OTH)

AF:

0.000143

AC:

AN:

27922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.0000686

AC:

AN:

145856

Hom.:

Cov.:

AF XY:

0.0000423

AC XY:

AN XY:

70912

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40458

American (AMR)

AF:

0.00

AC:

AN:

14724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

5066

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.000152

AC:

AN:

65816

Other (OTH)

AF:

0.00

AC:

AN:

2004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.26

Mutation Taster

=88/12

polymorphism

(source)

Splicing

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.

5-73447202-GGCGGCGGCGGCCTGC-GGCGGCGGCGGCCTGCGCGGCGGCGGCCTGC

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