Variant chr6-35455712-A-G 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.249-35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,610,456 control chromosomes in the GnomAD database, including 386,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42370 hom., cov: 31)

Exomes 𝑓: 0.69 ( 344431 hom. )

Consequence

FANCE
NM_021922.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.69

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=-0.83).

BP6

Variant 6-35455712-A-G is Benign according to our data. Variant chr6-35455712-A-G is described in ClinVar as [Benign]. Clinvar id is 261434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCE	NM_021922.3 linkuse as main transcript	c.249-35A>G		intron_variant		ENST00000229769.3	NP_068741.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
FANCE	ENST00000229769.3 linkuse as main transcript	c.249-35A>G	intron_variant	1	NM_021922.3	ENSP00000229769	P1
FANCE	ENST00000696264.1 linkuse as main transcript	c.249-35A>G	intron_variant			ENSP00000512511
FANCE	ENST00000648059.1 linkuse as main transcript	c.249-35A>G	intron_variant, NMD_transcript_variant			ENSP00000497902
FANCE	ENST00000696265.1 linkuse as main transcript	c.249-35A>G	intron_variant, NMD_transcript_variant			ENSP00000512512

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112591

AN:

151894

Hom.:

42316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.865

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.764

Gnomad ASJ

AF:

0.736

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.744

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.740

GnomAD3 exomes

AF:

0.721

AC:

179596

AN:

249262

Hom.:

65313

AF XY:

0.713

AC XY:

96111

AN XY:

134886

show subpopulations

Gnomad AFR exome

AF:

0.867

Gnomad AMR exome

AF:

0.820

Gnomad ASJ exome

AF:

0.735

Gnomad EAS exome

AF:

0.682

Gnomad SAS exome

AF:

0.747

Gnomad FIN exome

AF:

0.690

Gnomad NFE exome

AF:

0.673

Gnomad OTH exome

AF:

0.705

GnomAD4 exome

AF:

0.685

AC:

999514

AN:

1458444

Hom.:

344431

Cov.:

AF XY:

0.686

AC XY:

497693

AN XY:

725636

show subpopulations

Gnomad4 AFR exome

AF:

0.872

Gnomad4 AMR exome

AF:

0.814

Gnomad4 ASJ exome

AF:

0.732

Gnomad4 EAS exome

AF:

0.707

Gnomad4 SAS exome

AF:

0.742

Gnomad4 FIN exome

AF:

0.692

Gnomad4 NFE exome

AF:

0.667

Gnomad4 OTH exome

AF:

0.699

GnomAD4 genome

AF:

0.741

AC:

112703

AN:

152012

Hom.:

42370

Cov.:

AF XY:

0.742

AC XY:

55088

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.865

Gnomad4 AMR

AF:

0.765

Gnomad4 ASJ

AF:

0.736

Gnomad4 EAS

AF:

0.684

Gnomad4 SAS

AF:

0.743

Gnomad4 FIN

AF:

0.696

Gnomad4 NFE

AF:

0.674

Gnomad4 OTH

AF:

0.742

Alfa

AF:

0.688

Hom.:

74201

Bravo

AF:

0.754

Asia WGS

AF:

0.738

AC:

2565

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group E

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.0

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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