Genetic Variant ENST00000418244.7:n.88C>A (chr1-63322420-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000418244.7(FOXD3-AS1):n.88C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 985,574 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 4 hom. )

Consequence

FOXD3-AS1
ENST00000418244.7 non_coding_transcript_exon

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -3.26

Publications

4 publications found

Variant links:

Genes affected

FOXD3-AS1 (HGNC:40241): (FOXD3 antisense RNA 1)

FOXD3-AS1 links:

ENSG00000293613 (HGNC:):

ENSG00000293613 links:

ITGB3BP (HGNC:6157): (integrin subunit beta 3 binding protein) This gene encodes a transcriptional coregulator that binds to and enhances the activity of members of the nuclear receptor families, thyroid hormone receptors and retinoid X receptors. This protein also acts as a corepressor of NF-kappaB-dependent signaling. This protein induces apoptosis in breast cancer cells through a caspase 2-mediated signaling pathway. This protein is also a component of the centromere-specific histone H3 variant nucleosome associated complex (CENP-NAC) and may be involved in mitotic progression by recruiting the histone H3 variant CENP-A to the centromere. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ITGB3BP links:

FOXD3 (HGNC:3804): (forkhead box D3) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. Mutations in this gene cause autoimmune susceptibility 1. [provided by RefSeq, Nov 2008]

FOXD3 Gene-Disease associations (from GenCC):

anterior segment dysgenesis
Inheritance: AD Classification: LIMITED Submitted by: G2P
aniridia
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

FOXD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD3	NM_012183.3 link	c.-639G>T		upstream_gene_variant		ENST00000371116.4	NP_036315.1	Q9UJU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD3	ENST00000371116.4 link	c.-639G>T		upstream_gene_variant		6	NM_012183.3	ENSP00000360157.2		Q9UJU5

Frequencies

GnomAD3 genomes

AF:

0.00134

AC:

204

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.00190

AC:

1579

AN:

833200

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

773

AN XY:

384788

show subpopulations

African (AFR)

AF:

0.000127

AC:

AN:

15786

American (AMR)

AF:

0.00203

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.00272

AC:

AN:

5152

East Asian (EAS)

AF:

0.00

AC:

AN:

3634

South Asian (SAS)

AF:

0.0113

AC:

186

AN:

16466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

278

Middle Eastern (MID)

AF:

0.0142

AC:

AN:

1622

European-Non Finnish (NFE)

AF:

0.00163

AC:

1243

AN:

761976

Other (OTH)

AF:

0.00399

AC:

109

AN:

27302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

197

295

394

492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152374

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41596

American (AMR)

AF:

0.000522

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00691

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00952

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00169

AC:

115

AN:

68036

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.00107

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autoimmune disease, susceptibility to, 1

Other:1

Aug 01, 2005

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

1.7

(source)

DANN

Benign

0.94

PhyloP100

-3.3

PromoterAI

-0.056

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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ENST00000418244.7:n.88C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over