5-73447202-GGCGGCGGCGGCCTGC-GGCGGCGGCGGCCTGCGCGGCGGCGGCCTGC

Variant names:

• chr5-73447202-G-GGCGGCGGCGGCCTGC
• rs771204220
• NM_004472.3:c.1146_1160dupGCAGGCCGCCGCCGC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4 BS2

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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_004472.3.
• BS2: High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD1	NM_004472.3	c.1146_1160dupGCAGGCCGCCGCCGC	p.Ala387_Ala388insGlnAlaAlaAlaAla	disruptive_inframe_insertion	Exon 1 of 1	ENST00000615637.3	NP_004463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD1	ENST00000615637.3	c.1146_1160dupGCAGGCCGCCGCCGC	p.Ala387_Ala388insGlnAlaAlaAlaAla	disruptive_inframe_insertion	Exon 1 of 1	6	NM_004472.3	ENSP00000481581.1
FOXD1	ENST00000513595.1	n.-229_-215dupGCAGGCCGCCGCCGC		upstream_gene_variant		3
FOXD1-AS1	ENST00000514661.1	n.*218_*219insGCGGCGGCGGCCTGC		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0000686 AC: 10 AN: 145856 Hom.: 0 Cov.: 32

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.: 0 Cov.: 30 AF XY: 0.000122 AC XY: 48 AN XY: 393836

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000743

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: 0.000131

Gnomad4 OTH exome AF: 0.000143

GnomAD4 genome AF: 0.0000686 AC: 10 AN: 145856 Hom.: 0 Cov.: 32 AF XY: 0.0000423 AC XY: 3 AN XY: 70912

Gnomad4 AFR AF: 0.00

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: 0.000152

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs771204220; hg19: chr5-72743029;