rs186563531

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_StrongBS1BS2

The NM_021922.3(FANCE):c.248+7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,314,008 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 4 hom. )

Consequence

FANCE
NM_021922.3 splice_region, intron

Scores

Splicing: ADA: 0.00004310

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.282

Publications

0 publications found

Variant links:

COSMIC-nc: COSV104566736

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=-0.77).

BP6

Variant 6-35452800-C-A is Benign according to our data. Variant chr6-35452800-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 356443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00269 (410/152348) while in subpopulation AFR AF = 0.00707 (294/41598). AF 95% confidence interval is 0.0064. There are 1 homozygotes in GnomAd4. There are 204 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCE	NM_021922.3 link	c.248+7C>A		splice_region_variant, intron_variant	Intron 1 of 9	ENST00000229769.3	NP_068741.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
FANCE	ENST00000229769.3 link	c.248+7C>A	splice_region_variant, intron_variant	Intron 1 of 9	1	NM_021922.3	ENSP00000229769.2
FANCE	ENST00000696264.1 link	c.248+7C>A	splice_region_variant, intron_variant	Intron 1 of 7			ENSP00000512511.1
FANCE	ENST00000648059.1 link	n.248+7C>A	splice_region_variant, intron_variant	Intron 1 of 10			ENSP00000497902.1
FANCE	ENST00000696265.1 link	n.248+7C>A	splice_region_variant, intron_variant	Intron 1 of 8			ENSP00000512512.1

Frequencies

GnomAD3 genomes

AF:

0.00268

AC:

408

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00704

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.000912

AC:

AN:

36180

AF XY:

0.000732

show subpopulations

Gnomad AFR exome

AF:

0.0133

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00125

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000322

Gnomad NFE exome

AF:

0.000868

Gnomad OTH exome

AF:

0.000951

GnomAD4 exome

AF:

0.000791

AC:

919

AN:

1161660

Hom.:

Cov.:

AF XY:

0.000787

AC XY:

443

AN XY:

563062

show subpopulations

African (AFR)

AF:

0.00810

AC:

198

AN:

24436

American (AMR)

AF:

0.00235

AC:

AN:

14924

Ashkenazi Jewish (ASJ)

AF:

0.00158

AC:

AN:

17724

East Asian (EAS)

AF:

0.00

AC:

AN:

27084

South Asian (SAS)

AF:

0.000292

AC:

AN:

44488

European-Finnish (FIN)

AF:

0.000269

AC:

AN:

26000

Middle Eastern (MID)

AF:

0.00311

AC:

AN:

3214

European-Non Finnish (NFE)

AF:

0.000564

AC:

540

AN:

957174

Other (OTH)

AF:

0.00189

AC:

AN:

46616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

138

184

230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00269

AC:

410

AN:

152348

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00707

AC:

294

AN:

41598

American (AMR)

AF:

0.00229

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68016

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000884

Hom.:

Bravo

AF:

0.00335

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group E

Benign:4

Aug 20, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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:1

Nov 19, 2021

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia

Benign:1

Apr 26, 2021

Sema4, Sema4

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.3

(source)

DANN

Benign

0.79

PhyloP100

0.28

PromoterAI

0.032

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000043

dbscSNV1_RF

Benign

0.0

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