NM_021922.3:c.900+39A>G

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.900+39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,608,134 control chromosomes in the GnomAD database, including 229,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 16463 hom., cov: 31)

Exomes 𝑓: 0.53 ( 212589 hom. )

Consequence

FANCE
NM_021922.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: -0.633

Publications

17 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=-0.84).

BP6

Variant 6-35457639-A-G is Benign according to our data. Variant chr6-35457639-A-G is described in ClinVar as Benign. ClinVar VariationId is 261436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCE	NM_021922.3 link	c.900+39A>G		intron_variant	Intron 3 of 9	ENST00000229769.3	NP_068741.1	Q9HB96

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCE	ENST00000229769.3 link	c.900+39A>G		intron_variant	Intron 3 of 9	1	NM_021922.3	ENSP00000229769.2		Q9HB96

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64612

AN:

151938

Hom.:

16449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.521

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.354

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.609

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.559

Gnomad OTH

AF:

0.406

GnomAD2 exomes

AF:

0.502

AC:

124083

AN:

247226

AF XY:

0.500

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.632

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.357

Gnomad FIN exome

AF:

0.601

Gnomad NFE exome

AF:

0.555

Gnomad OTH exome

AF:

0.498

GnomAD4 exome

AF:

0.532

AC:

775236

AN:

1456078

Hom.:

212589

Cov.:

AF XY:

0.529

AC XY:

383380

AN XY:

724532

show subpopulations

African (AFR)

AF:

0.115

AC:

3842

AN:

33414

American (AMR)

AF:

0.616

AC:

27401

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

9144

AN:

26092

East Asian (EAS)

AF:

0.381

AC:

15115

AN:

39650

South Asian (SAS)

AF:

0.430

AC:

36969

AN:

85954

European-Finnish (FIN)

AF:

0.601

AC:

31462

AN:

52370

Middle Eastern (MID)

AF:

0.390

AC:

2247

AN:

5758

European-Non Finnish (NFE)

AF:

0.559

AC:

619920

AN:

1108114

Other (OTH)

AF:

0.484

AC:

29136

AN:

60226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

19658

39316

58975

78633

98291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17076

34152

51228

68304

85380

<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:

0.425

AC:

64641

AN:

152056

Hom.:

16463

Cov.:

AF XY:

0.427

AC XY:

31693

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.138

AC:

5746

AN:

41492

American (AMR)

AF:

0.521

AC:

7956

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1225

AN:

3468

East Asian (EAS)

AF:

0.354

AC:

1827

AN:

5158

South Asian (SAS)

AF:

0.427

AC:

2061

AN:

4824

European-Finnish (FIN)

AF:

0.609

AC:

6438

AN:

10572

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.559

AC:

37993

AN:

67966

Other (OTH)

AF:

0.404

AC:

850

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1646

3292

4939

6585

8231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.475

Hom.:

3999

Bravo

AF:

0.404

Asia WGS

AF:

0.340

AC:

1185

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Jan 10, 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. -

Fanconi anemia complementation group E

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

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

-0.84

CADD

Benign

0.19

(source)

DANN

Benign

0.81

PhyloP100

-0.63

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