Variant rs6457823 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:4

Conservation

PhyloP100: -4.73

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
FANCE	NM_021922.3 linkuse as main transcript	c.1316+19G>A		intron_variant		ENST00000229769.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCE	ENST00000229769.3 linkuse as main transcript	c.1316+19G>A		intron_variant		1	NM_021922.3	P1

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

GnomAD3 exomes

AF:

0.0905

AC:

22746

AN:

251320

Hom.:

1950

AF XY:

0.0893

AC XY:

12134

AN XY:

135848

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 SAS exome

AF:

0.161

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

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.0552

Gnomad4 ASJ exome

AF:

0.0663

Gnomad4 EAS exome

AF:

0.0832

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.0371

Gnomad4 NFE exome

AF:

0.0511

Gnomad4 OTH exome

AF:

0.0879

GnomAD4 genome

AF:

0.144

AC:

21861

AN:

152114

Hom.:

2924

Cov.:

AF XY:

0.142

AC XY:

10570

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.358

Gnomad4 AMR

AF:

0.0735

Gnomad4 ASJ

AF:

0.0729

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.0334

Gnomad4 NFE

AF:

0.0531

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.100

Hom.:

312

Bravo

AF:

0.156

Asia WGS

AF:

0.173

AC:

601

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

Uncertain significance, no assertion criteria provided	curation	Leiden Open Variation Database	Feb 28, 2020	Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -

Fanconi anemia complementation group E

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

0.0040

Dann

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over