chr1-47438286-G-C

Variant names:

• chr1-47438286-G-C
• rs1570416865
• NM_004474.4:c.151G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004474.4(FOXD2):​c.151G>C​(p.Val51Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000842 in 1,187,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V51M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: FOXD2 NM_004474.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 0 publications found

Genes affected

FOXD2 (HGNC:3803): (forkhead box D2) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12903571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD2	NM_004474.4	c.151G>C	p.Val51Leu	missense_variant	Exon 1 of 1	ENST00000334793.6	NP_004465.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD2	ENST00000334793.6	c.151G>C	p.Val51Leu	missense_variant	Exon 1 of 1	6	NM_004474.4	ENSP00000335493.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.42e-7 AC: 1 AN: 1187556 Hom.: 0 Cov.: 30 AF XY: 0.00000174 AC XY: 1 AN XY: 576152

African (AFR) AF: 0.00 AC: 0 AN: 23918

American (AMR) AF: 0.00 AC: 0 AN: 10454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16660

East Asian (EAS) AF: 0.00 AC: 0 AN: 27124

South Asian (SAS) AF: 0.00 AC: 0 AN: 49164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3552

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 979956

Other (OTH) AF: 0.00 AC: 0 AN: 48010

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.79
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.40	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.31
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.18
Sift	Benign	0.47	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.035
MutPred		0.22		Gain of helix (P = 0.0854);
MVP		0.57
ClinPred		0.030	T
GERP RS		2.1
PromoterAI		0.0094	Neutral
Varity_R		0.069
gMVP		0.15
Mutation Taster		=82/18	polymorphism

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: rs1570416865; hg19: chr1-47903958;