rs6457823

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1316+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 1,609,688 control chromosomes in the GnomAD database, including 8,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2924 hom., cov: 31)

Exomes 𝑓: 0.067 ( 5876 hom. )

Consequence

FANCE
NM_021922.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: -4.73

Publications

10 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 (BayesDel_noAF=-0.9).

BP6

Variant 6-35459779-G-A is Benign according to our data. Variant chr6-35459779-G-A is described in ClinVar as Benign. ClinVar VariationId is 261433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCE	NM_021922.3 link	c.1316+19G>A		intron_variant	Intron 7 of 9	ENST00000229769.3	NP_068741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCE	ENST00000229769.3 link	c.1316+19G>A		intron_variant	Intron 7 of 9	1	NM_021922.3	ENSP00000229769.2

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21822

AN:

151996

Hom.:

2913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.358

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0737

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:

0.0531

Gnomad OTH

AF:

0.127

GnomAD2 exomes

AF:

0.0905

AC:

22746

AN:

251320

AF XY:

0.0893

show subpopulations

Gnomad AFR exome

AF:

0.367

Gnomad AMR exome

AF:

0.0512

Gnomad ASJ exome

AF:

0.0669

Gnomad EAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.0370

Gnomad NFE exome

AF:

0.0538

Gnomad OTH exome

AF:

0.0705

GnomAD4 exome

AF:

0.0675

AC:

98361

AN:

1457574

Hom.:

5876

Cov.:

AF XY:

0.0693

AC XY:

50244

AN XY:

725396

show subpopulations

African (AFR)

AF:

0.379

AC:

12638

AN:

33356

American (AMR)

AF:

0.0552

AC:

2469

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0663

AC:

1732

AN:

26110

East Asian (EAS)

AF:

0.0832

AC:

3303

AN:

39680

South Asian (SAS)

AF:

0.161

AC:

13838

AN:

86160

European-Finnish (FIN)

AF:

0.0371

AC:

1981

AN:

53408

Middle Eastern (MID)

AF:

0.0799

AC:

460

AN:

5760

European-Non Finnish (NFE)

AF:

0.0511

AC:

56644

AN:

1108132

Other (OTH)

AF:

0.0879

AC:

5296

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

4286

8571

12857

17142

21428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2378

4756

7134

9512

11890

<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:

21861

AN:

152114

Hom.:

2924

Cov.:

AF XY:

0.142

AC XY:

10570

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.358

AC:

14812

AN:

41418

American (AMR)

AF:

0.0735

AC:

1123

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0729

AC:

253

AN:

3472

East Asian (EAS)

AF:

0.114

AC:

591

AN:

5176

South Asian (SAS)

AF:

0.167

AC:

807

AN:

4826

European-Finnish (FIN)

AF:

0.0334

AC:

354

AN:

10610

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0531

AC:

3610

AN:

68010

Other (OTH)

AF:

0.133

AC:

280

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

796

1592

2389

3185

3981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.106

Hom.:

354

Bravo

AF:

0.156

Asia WGS

AF:

0.173

AC:

601

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group E

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Nov 06, 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

Feb 28, 2020

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. -

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.90

CADD

Benign

0.0040

(source)

DANN

Benign

0.51

PhyloP100

-4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over