5-73447175-CGGCGAG-CGGCGAGGGCGAG

Variant names:

• chr5-73447175-C-CGGCGAG
• rs892625814
• NM_004472.3:c.1182_1187dupCTCGCC

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM4 BP6 BS2

The NM_004472.3(FOXD1):​c.1182_1187dupCTCGCC​(p.Pro396_Val397insSerPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00479 in 1,063,614 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0036 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (12 hom.)
• Consequence: FOXD1 NM_004472.3 disruptive_inframe_insertion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.573
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_004472.3.
• BP6: Variant 5-73447175-C-CGGCGAG is Benign according to our data. Variant chr5-73447175-C-CGGCGAG is described in ClinVar as Likely_benign. ClinVar VariationId is 3029712.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 522 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.1182_1187dupCTCGCC	p.Pro396_Val397insSerPro	disruptive_inframe_insertion	Exon 1 of 1	NP_004463.1	Q16676

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXD1	ENST00000615637.3	TSL:6 MANE Select	c.1182_1187dupCTCGCC	p.Pro396_Val397insSerPro	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000481581.1	Q16676
	FOXD1	ENST00000513595.1	TSL:3	n.-193_-188dupCTCGCC		upstream_gene	N/A
	FOXD1-AS1	ENST00000514661.1	TSL:3	n.*191_*192insGGCGAG		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 521 AN: 146576 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.0155

Gnomad AMR AF: 0.00758

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00456

Gnomad OTH AF: 0.00742

GnomAD4 exome AF: 0.00499 AC: 4576 AN: 916932 Hom.: 12 Cov.: 33 AF XY: 0.00493 AC XY: 2127 AN XY: 431388

African (AFR) AF: 0.00245 AC: 43 AN: 17554

American (AMR) AF: 0.00573 AC: 18 AN: 3140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7384

East Asian (EAS) AF: 0.00 AC: 0 AN: 9688

South Asian (SAS) AF: 0.000220 AC: 4 AN: 18176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9572

Middle Eastern (MID) AF: 0.000994 AC: 2 AN: 2012

European-Non Finnish (NFE) AF: 0.00534 AC: 4362 AN: 817420

Other (OTH) AF: 0.00460 AC: 147 AN: 31986

GnomAD4 genome AF: 0.00356 AC: 522 AN: 146682 Hom.: 1 Cov.: 32 AF XY: 0.00318 AC XY: 227 AN XY: 71410

African (AFR) AF: 0.00193 AC: 79 AN: 40956

American (AMR) AF: 0.00757 AC: 112 AN: 14788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 5042

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8500

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.00456 AC: 301 AN: 65968

Other (OTH) AF: 0.00734 AC: 15 AN: 2044

Alfa AF: 0.000109 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FOXD1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.57
Mutation Taster		=88/12	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs892625814; hg19: chr5-72743002;