rs771204220

Variant names:

• chr5-73447202-GGCGGCGGCGGCCTGC-G
• rs771204220
• NM_004472.3:c.1146_1160delGCAGGCCGCCGCCGC

Your query was ambiguous. Multiple possible variants found:

• chr5-73447202-GGCGGCGGCGGCCTGC-G
• chr5-73447202-GGCGGCGGCGGCCTGC-GGCGGCGGCGGCCTGCGCGGCGGCGGCCTGC

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM4 BP6 BA1

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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.12
• Publications: 1 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: Benign. The variant received -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 VariationId is 3042166.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.05 is higher than 0.05.

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_1160delGCAGGCCGCCGCCGC	p.Gln383_Ala387del	disruptive_inframe_deletion	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.1146_1160delGCAGGCCGCCGCCGC	p.Gln383_Ala387del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000481581.1	Q16676
	FOXD1	ENST00000513595.1	TSL:3	n.-229_-215delGCAGGCCGCCGCCGC		upstream_gene	N/A
	FOXD1-AS1	ENST00000514661.1	TSL:3	n.*219_*233delGCGGCGGCGGCCTGC		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4312 AN: 145828 Hom.: 96 Cov.: 31

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

GnomAD2 exomes AF: 0.0224 AC: 3 AN: 134 AF XY: 0.0385

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

African (AFR) AF: 0.00443 AC: 70 AN: 15794

American (AMR) AF: 0.0394 AC: 53 AN: 1346

Ashkenazi Jewish (ASJ) AF: 0.0157 AC: 84 AN: 5342

East Asian (EAS) AF: 0.000726 AC: 3 AN: 4132

South Asian (SAS) AF: 0.0298 AC: 519 AN: 17442

European-Finnish (FIN) AF: 0.0354 AC: 43 AN: 1214

Middle Eastern (MID) AF: 0.0293 AC: 49 AN: 1670

European-Non Finnish (NFE) AF: 0.0505 AC: 38943 AN: 771880

Other (OTH) AF: 0.0414 AC: 1155 AN: 27920

GnomAD4 genome AF: 0.0295 AC: 4311 AN: 145936 Hom.: 96 Cov.: 31 AF XY: 0.0276 AC XY: 1963 AN XY: 71022

African (AFR) AF: 0.00818 AC: 332 AN: 40576

American (AMR) AF: 0.0263 AC: 388 AN: 14744

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 45 AN: 3392

East Asian (EAS) AF: 0.000990 AC: 5 AN: 5050

South Asian (SAS) AF: 0.0260 AC: 125 AN: 4814

European-Finnish (FIN) AF: 0.0291 AC: 243 AN: 8360

Middle Eastern (MID) AF: 0.00704 AC: 2 AN: 284

European-Non Finnish (NFE) AF: 0.0460 AC: 3025 AN: 65780

Other (OTH) AF: 0.0257 AC: 52 AN: 2026

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0271

ClinVar

ClinVar submissions

Significance: 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		2.1
Mutation Taster		=189/11	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs771204220; hg19: chr5-72743029; COSMIC: COSV105903775; COSMIC: COSV105903775;