rs4713867

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021922.3(FANCE):c.387A>C(p.Pro129Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,613,928 control chromosomes in the GnomAD database, including 388,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P129P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.74 ( 42628 hom., cov: 32)

Exomes 𝑓: 0.69 ( 345414 hom. )

Consequence

FANCE
NM_021922.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:7

Conservation

PhyloP100: -1.10

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-35455885-A-C is Benign according to our data. Variant chr6-35455885-A-C is described in ClinVar as Benign. ClinVar VariationId is 261435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCE	NM_021922.3 link	c.387A>C	p.Pro129Pro	synonymous_variant	Exon 2 of 10	ENST00000229769.3	NP_068741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCE	ENST00000229769.3 link	c.387A>C	p.Pro129Pro	synonymous_variant	Exon 2 of 10	1	NM_021922.3	ENSP00000229769.2

Frequencies

GnomAD3 genomes

AF:

0.743

AC:

112920

AN:

152008

Hom.:

42567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.871

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.767

Gnomad ASJ

AF:

0.739

Gnomad EAS

AF:

0.685

Gnomad SAS

AF:

0.744

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.740

GnomAD2 exomes

AF:

0.721

AC:

181094

AN:

251214

AF XY:

0.713

show subpopulations

Gnomad AFR exome

AF:

0.872

Gnomad AMR exome

AF:

0.821

Gnomad ASJ exome

AF:

0.736

Gnomad EAS exome

AF:

0.682

Gnomad FIN exome

AF:

0.690

Gnomad NFE exome

AF:

0.673

Gnomad OTH exome

AF:

0.704

GnomAD4 exome

AF:

0.686

AC:

1002192

AN:

1461802

Hom.:

345414

Cov.:

AF XY:

0.686

AC XY:

498993

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.877

AC:

29362

AN:

33480

American (AMR)

AF:

0.815

AC:

36453

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.733

AC:

19163

AN:

26136

East Asian (EAS)

AF:

0.707

AC:

28075

AN:

39700

South Asian (SAS)

AF:

0.743

AC:

64077

AN:

86256

European-Finnish (FIN)

AF:

0.691

AC:

36897

AN:

53366

Middle Eastern (MID)

AF:

0.707

AC:

4080

AN:

5768

European-Non Finnish (NFE)

AF:

0.667

AC:

741820

AN:

1111978

Other (OTH)

AF:

0.700

AC:

42265

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

20136

40273

60409

80546

100682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19314

38628

57942

77256

96570

<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:

0.743

AC:

113041

AN:

152126

Hom.:

42628

Cov.:

AF XY:

0.743

AC XY:

55268

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.871

AC:

36162

AN:

41524

American (AMR)

AF:

0.767

AC:

11725

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.739

AC:

2566

AN:

3470

East Asian (EAS)

AF:

0.685

AC:

3533

AN:

5154

South Asian (SAS)

AF:

0.743

AC:

3583

AN:

4820

European-Finnish (FIN)

AF:

0.696

AC:

7354

AN:

10572

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.674

AC:

45791

AN:

67980

Other (OTH)

AF:

0.742

AC:

1565

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1454

2909

4363

5818

7272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.693

Hom.:

17921

Bravo

AF:

0.756

Asia WGS

AF:

0.738

AC:

2567

AN:

3478

EpiCase

AF:

0.670

EpiControl

AF:

0.671

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group E

Benign:5

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

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.

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Uncertain:1Benign:1

Jan 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.24

(source)

DANN

Benign

0.39

PhyloP100

-1.1

Mutation Taster

=100/0

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