Genetic Variant FANCE:c.900+39A>G (chr6-35457639-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).

BP6

Variant 6-35457639-A-G is Benign according to our data. Variant chr6-35457639-A-G is described in ClinVar as [Benign]. Clinvar id 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

GnomAD3 exomes

AF:

0.502

AC:

124083

AN:

247226

Hom.:

33305

AF XY:

0.500

AC XY:

66884

AN XY:

133706

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 SAS exome

AF:

0.430

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

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.616

Gnomad4 ASJ exome

AF:

0.350

Gnomad4 EAS exome

AF:

0.381

Gnomad4 SAS exome

AF:

0.430

Gnomad4 FIN exome

AF:

0.601

Gnomad4 NFE exome

AF:

0.559

Gnomad4 OTH exome

AF:

0.484

GnomAD4 genome

AF:

0.425

AC:

64641

AN:

152056

Hom.:

16463

Cov.:

AF XY:

0.427

AC XY:

31693

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.521

Gnomad4 ASJ

AF:

0.353

Gnomad4 EAS

AF:

0.354

Gnomad4 SAS

AF:

0.427

Gnomad4 FIN

AF:

0.609

Gnomad4 NFE

AF:

0.559

Gnomad4 OTH

AF:

0.404

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

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. -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fanconi anemia complementation group E

Benign:2

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

- -

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

DANN

Benign

0.81

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

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