dbSNP rs372116111: FOXD4L1:p.Pro175Arg (chr2-113499780-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_012184.5(FOXD4L1):c.524C>G(p.Pro175Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000114 in 1,535,594 control chromosomes in the GnomAD database, including 28 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 5 hom., cov: 28)

Exomes 𝑓: 0.00011 ( 23 hom. )

Consequence

FOXD4L1
NM_012184.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.65

Publications

0 publications found

Variant links:

Genes affected

FOXD4L1 (HGNC:18521): (forkhead box D4 like 1) This gene is a member of the forkhead/winged-helix (FOX) family of transcription factors with highly conserved FOX DNA-binding domains. Members of the FOX family of transcription factors are regulators of embryogenesis and may play a role in human cancer. This gene lies in a region of chromosome 2 that surrounds the site where two ancestral chromosomes fused to form human chromosome 2. This region is duplicated elsewhere in the human genome, primarily in subtelomeric and pericentromeric locations, thus mutiple copies of this gene have been found. [provided by RefSeq, Jul 2008]

FOXD4L1 links:

ENSG00000304550 (HGNC:):

ENSG00000304550 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BS2

High Homozygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012184.5. 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
	FOXD4L1	NM_012184.5	MANE Select	c.524C>G	p.Pro175Arg	missense	Exon 1 of 1	NP_036316.1	Q9NU39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXD4L1	ENST00000306507.7	TSL:6 MANE Select	c.524C>G	p.Pro175Arg	missense	Exon 1 of 1	ENSP00000302756.5	Q9NU39
	ENSG00000304550	ENST00000804501.1		n.691+2179G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

141498

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000170

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000261

AC:

AN:

229764

AF XY:

0.0000318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000556

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000115

AC:

160

AN:

1394096

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

694818

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32654

American (AMR)

AF:

0.00

AC:

AN:

38926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25714

East Asian (EAS)

AF:

0.00

AC:

AN:

32332

South Asian (SAS)

AF:

0.00

AC:

AN:

83208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4992

European-Non Finnish (NFE)

AF:

0.000144

AC:

154

AN:

1067618

Other (OTH)

AF:

0.000104

AC:

AN:

57580

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000106

AC:

AN:

141498

Hom.:

Cov.:

AF XY:

0.0000437

AC XY:

AN XY:

68612

show subpopulations

African (AFR)

AF:

0.000101

AC:

AN:

39444

American (AMR)

AF:

0.00

AC:

AN:

13462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3366

East Asian (EAS)

AF:

0.00

AC:

AN:

3562

South Asian (SAS)

AF:

0.00

AC:

AN:

4278

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.000170

AC:

AN:

64516

Other (OTH)

AF:

0.00

AC:

AN:

1936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000131

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.00000863

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.72

MetaSVM

Pathogenic

0.94

MutationAssessor

Uncertain

2.8

PhyloP100

5.6

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-9.0

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.55

MVP

0.94

ClinPred

0.97

GERP RS

2.6

Varity_R

0.70

gMVP

0.15

Mutation Taster

=89/11

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over