Genetic Variant NM_012184.5:c.257G>A (chr2-113499513-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012184.5(FOXD4L1):c.257G>A(p.Gly86Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000362 in 1,602,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FOXD4L1
NM_012184.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0570

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.012772441).

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.257G>A	p.Gly86Asp	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.257G>A	p.Gly86Asp	missense	Exon 1 of 1	ENSP00000302756.5	Q9NU39
	ENSG00000304550	ENST00000804501.1		n.691+2446C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

142784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000708

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000146

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:

0.00

Gnomad OTH

AF:

0.000508

GnomAD2 exomes

AF:

0.0000720

AC:

AN:

236220

AF XY:

0.0000466

show subpopulations

Gnomad AFR exome

AF:

0.00111

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1459820

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726236

show subpopulations

African (AFR)

AF:

0.000539

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4252

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111908

Other (OTH)

AF:

0.000116

AC:

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000217

AC:

AN:

142906

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

AN XY:

69430

show subpopulations

African (AFR)

AF:

0.000705

AC:

AN:

39698

American (AMR)

AF:

0.000146

AC:

AN:

13728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3398

East Asian (EAS)

AF:

0.00

AC:

AN:

3792

South Asian (SAS)

AF:

0.00

AC:

AN:

4306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64940

Other (OTH)

AF:

0.000503

AC:

AN:

1990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000571

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.000923

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000125

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

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.41

M_CAP

Benign

0.040

MetaRNN

Benign

0.013

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.6

PhyloP100

-0.057

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.3

REVEL

Benign

0.16

Sift

Benign

0.057

Sift4G

Uncertain

0.043

Polyphen

0.42

Vest4

0.071

MVP

0.66

ClinPred

0.011

GERP RS

0.56

Varity_R

0.052

gMVP

0.13

Mutation Taster

=100/0

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