dbSNP rs199845792: FOXD4L1:p.Ile155Val (chr2-113499719-A-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6

The NM_012184.5(FOXD4L1):c.463A>G(p.Ile155Val) variant causes a missense change. The variant allele was found at a frequency of 0.00103 in 140,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0090 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXD4L1
NM_012184.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.62

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08063957).

BP6

Variant 2-113499719-A-G is Benign according to our data. Variant chr2-113499719-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2681285.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD4L1	NM_012184.5 link	c.463A>G	p.Ile155Val	missense_variant	Exon 1 of 1	ENST00000306507.7	NP_036316.1	Q9NU39B3KVK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD4L1	ENST00000306507.7 link	c.463A>G	p.Ile155Val	missense_variant	Exon 1 of 1	6	NM_012184.5	ENSP00000302756.5		Q9NU39

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

144

AN:

139988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.000299

Gnomad EAS

AF:

0.000485

Gnomad SAS

AF:

0.000938

Gnomad FIN

AF:

0.000719

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.00102

Gnomad OTH

AF:

0.00157

GnomAD3 exomes

AF:

0.000509

AC:

117

AN:

229830

Hom.:

AF XY:

0.000460

AC XY:

AN XY:

126096

show subpopulations

Gnomad AFR exome

AF:

0.000140

Gnomad AMR exome

AF:

0.000483

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.0000653

Gnomad SAS exome

AF:

0.000173

Gnomad FIN exome

AF:

0.00295

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00905

AC:

11795

AN:

1303350

Hom.:

Cov.:

AF XY:

0.00863

AC XY:

5615

AN XY:

650508

show subpopulations

Gnomad4 AFR exome

AF:

0.00481

Gnomad4 AMR exome

AF:

0.0192

Gnomad4 ASJ exome

AF:

0.00210

Gnomad4 EAS exome

AF:

0.00222

Gnomad4 SAS exome

AF:

0.00467

Gnomad4 FIN exome

AF:

0.00994

Gnomad4 NFE exome

AF:

0.00967

Gnomad4 OTH exome

AF:

0.00675

GnomAD4 genome

AF:

0.00103

AC:

144

AN:

140090

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

AN XY:

68118

show subpopulations

Gnomad4 AFR

AF:

0.000697

Gnomad4 AMR

AF:

0.00249

Gnomad4 ASJ

AF:

0.000299

Gnomad4 EAS

AF:

0.000729

Gnomad4 SAS

AF:

0.000938

Gnomad4 FIN

AF:

0.000719

Gnomad4 NFE

AF:

0.00102

Gnomad4 OTH

AF:

0.00155

Alfa

AF:

0.00144

Hom.:

ExAC

AF:

0.000714

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma

Benign:1

Department of Clinical Pathology, School of Medicine, Fujita Health University

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.055

MetaRNN

Benign

0.081

MetaSVM

Pathogenic

0.92

MutationAssessor

Uncertain

2.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.0

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.33

MVP

0.99

ClinPred

0.046

GERP RS

2.6

Varity_R

0.25

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over