chr1-47438280-C-T

Variant names:

• chr1-47438280-C-T
• rs1335922879
• NM_004474.4:c.145C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004474.4(FOXD2):​c.145C>T​(p.Arg49Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000587 in 1,193,198 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: FOXD2 NM_004474.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004474.4. 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
	FOXD2	NM_004474.4	MANE Select	c.145C>T	p.Arg49Trp	missense	Exon 1 of 1	NP_004465.3	O60548

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXD2	ENST00000334793.6	TSL:6 MANE Select	c.145C>T	p.Arg49Trp	missense	Exon 1 of 1	ENSP00000335493.6	O60548

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000587 AC: 7 AN: 1193198 Hom.: 0 Cov.: 30 AF XY: 0.00000173 AC XY: 1 AN XY: 579600

African (AFR) AF: 0.00 AC: 0 AN: 23976

American (AMR) AF: 0.00 AC: 0 AN: 10750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16896

East Asian (EAS) AF: 0.000258 AC: 7 AN: 27174

South Asian (SAS) AF: 0.00 AC: 0 AN: 50282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 983338

Other (OTH) AF: 0.00 AC: 0 AN: 48312

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.063
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	1.0	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	0.34	N
PhyloP100		3.5
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.26
MutPred		0.23		Loss of methylation at R46 (P = 0.0303)
MVP		0.99
ClinPred		0.85	D
GERP RS		3.0
PromoterAI		0.010	Neutral
Varity_R		0.17
gMVP		0.31
Mutation Taster		=86/14	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: rs1335922879; hg19: chr1-47903952; COSMIC: COSV104641535; COSMIC: COSV104641535;