5-73447619-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004472.3(FOXD1):​c.744G>C​(p.Ala248Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 1,166,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A248A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: FOXD1 NM_004472.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• 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>C	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>C	p.Ala248Ala	synonymous	Exon 1 of 1	ENSP00000481581.1	Q16676

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000171 AC: 2 AN: 1166760 Hom.: 0 Cov.: 33 AF XY: 0.00000354 AC XY: 2 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: 0.00000207 AC: 2 AN: 966140

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.1
DANN	Benign	0.80
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;