chr5-73447619-C-A

Variant names:

• chr5-73447619-C-A
• rs921299597
• NM_004472.3:c.744G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_004472.3(FOXD1):​c.744G>T​(p.Ala248Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXD1 NM_004472.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.43
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 5-73447619-C-A is Benign according to our data. Variant chr5-73447619-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3032563.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.43 with no splicing effect.

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.744G>T	p.Ala248Ala	synonymous	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.744G>T	p.Ala248Ala	synonymous	Exon 1 of 1	ENSP00000481581.1	Q16676

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1166760 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 564642

African (AFR) AF: 0.00 AC: 0 AN: 22914

American (AMR) AF: 0.00 AC: 0 AN: 9186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15210

East Asian (EAS) AF: 0.00 AC: 0 AN: 26420

South Asian (SAS) AF: 0.00 AC: 0 AN: 38002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3148

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 966140

Other (OTH) AF: 0.00 AC: 0 AN: 46434

GnomAD4 genome Cov.: 32

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
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.0
DANN	Benign	0.92
PhyloP100		-1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs921299597; hg19: chr5-72743444;