rs9462088

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021922.3(FANCE):c.1504G>A(p.Ala502Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,614,066 control chromosomes in the GnomAD database, including 8,884 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2963 hom., cov: 32)

Exomes 𝑓: 0.068 ( 5921 hom. )

Consequence

FANCE
NM_021922.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:6O:1

Conservation

PhyloP100: 1.05

Publications

33 publications found

Variant links:

Genes affected

FANCE (HGNC:3586): (FA complementation group E) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group E. [provided by RefSeq, Jul 2008]

FANCE Gene-Disease associations (from GenCC):

Fanconi anemia complementation group E
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FANCE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035373569).

BP6

Variant 6-35462909-G-A is Benign according to our data. Variant chr6-35462909-G-A is described in ClinVar as Benign. ClinVar VariationId is 134345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCE	NM_021922.3 link	c.1504G>A	p.Ala502Thr	missense_variant	Exon 9 of 10	ENST00000229769.3	NP_068741.1	Q9HB96

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCE	ENST00000229769.3 link	c.1504G>A	p.Ala502Thr	missense_variant	Exon 9 of 10	1	NM_021922.3	ENSP00000229769.2		Q9HB96

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21930

AN:

152152

Hom.:

2952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.360

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0738

Gnomad ASJ

AF:

0.0729

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0334

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0530

Gnomad OTH

AF:

0.127

GnomAD2 exomes

AF:

0.0906

AC:

22784

AN:

251476

AF XY:

0.0894

show subpopulations

Gnomad AFR exome

AF:

0.369

Gnomad AMR exome

AF:

0.0513

Gnomad ASJ exome

AF:

0.0669

Gnomad EAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.0369

Gnomad NFE exome

AF:

0.0537

Gnomad OTH exome

AF:

0.0707

GnomAD4 exome

AF:

0.0676

AC:

98786

AN:

1461796

Hom.:

5921

Cov.:

AF XY:

0.0693

AC XY:

50420

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.381

AC:

12745

AN:

33476

American (AMR)

AF:

0.0553

AC:

2472

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0663

AC:

1734

AN:

26136

East Asian (EAS)

AF:

0.0832

AC:

3305

AN:

39700

South Asian (SAS)

AF:

0.161

AC:

13867

AN:

86256

European-Finnish (FIN)

AF:

0.0371

AC:

1980

AN:

53416

Middle Eastern (MID)

AF:

0.0799

AC:

460

AN:

5756

European-Non Finnish (NFE)

AF:

0.0512

AC:

56909

AN:

1111944

Other (OTH)

AF:

0.0880

AC:

5314

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

5286

10571

15857

21142

26428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2396

4792

7188

9584

11980

<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:

0.144

AC:

21969

AN:

152270

Hom.:

2963

Cov.:

AF XY:

0.143

AC XY:

10628

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.359

AC:

14914

AN:

41510

American (AMR)

AF:

0.0736

AC:

1127

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0729

AC:

253

AN:

3470

East Asian (EAS)

AF:

0.115

AC:

594

AN:

5184

South Asian (SAS)

AF:

0.167

AC:

808

AN:

4830

European-Finnish (FIN)

AF:

0.0334

AC:

355

AN:

10624

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0530

AC:

3608

AN:

68026

Other (OTH)

AF:

0.132

AC:

280

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

850

1700

2549

3399

4249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.0822

Hom.:

4802

Bravo

AF:

0.156

TwinsUK

AF:

0.0580

AC:

215

ALSPAC

AF:

0.0537

AC:

207

ESP6500AA

AF:

0.344

AC:

1514

ESP6500EA

AF:

0.0523

AC:

450

ExAC

AF:

0.0979

AC:

11882

Asia WGS

AF:

0.174

AC:

604

AN:

3478

EpiCase

AF:

0.0495

EpiControl

AF:

0.0535

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group E

Uncertain:1Benign:4

Feb 07, 2011

Leiden Open Variation Database

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:curation

Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. -

Nov 06, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.062

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

1.1

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.73

REVEL

Benign

0.050

Sift

Benign

0.89

Sift4G

Benign

0.53

Polyphen

0.0070

Vest4

0.043

MPC

0.14

ClinPred

0.0028

GERP RS

3.2

Varity_R

0.067

gMVP

0.046

Mutation Taster

=77/23

polymorphism (auto)

(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

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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