rs9462088

Positions:

chr6-35462909-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021922.3(FANCE):c.1504G>A(p.Ala502Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,614,066 control chromosomes in the GnomAD database, including 8,884 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2963 hom., cov: 32)

Exomes 𝑓: 0.068 ( 5921 hom. )

Consequence

FANCE
NM_021922.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:6O:1

Conservation

PhyloP100: 1.05

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:

FANCE (HGNC:):

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 (MetaRNN=0.0035373569).

BP6

Variant 6-35462909-G-A is Benign according to our data. Variant chr6-35462909-G-A is described in ClinVar as [Benign]. Clinvar id is 134345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 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.1504G>A	p.Ala502Thr	missense_variant	9/10	ENST00000229769.3	NP_068741.1	Q9HB96

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCE	ENST00000229769.3 linkuse as main transcript	c.1504G>A	p.Ala502Thr	missense_variant	9/10	1	NM_021922.3	ENSP00000229769.2		Q9HB96

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21930

AN:

152152

Hom.:

2952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.360

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0738

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:

0.0530

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.0906

AC:

22784

AN:

251476

Hom.:

1975

AF XY:

0.0894

AC XY:

12148

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.369

Gnomad AMR exome

AF:

0.0513

Gnomad ASJ exome

AF:

0.0669

Gnomad EAS exome

AF:

0.111

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.0369

Gnomad NFE exome

AF:

0.0537

Gnomad OTH exome

AF:

0.0707

GnomAD4 exome

AF:

0.0676

AC:

98786

AN:

1461796

Hom.:

5921

Cov.:

AF XY:

0.0693

AC XY:

50420

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.381

Gnomad4 AMR exome

AF:

0.0553

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:

0.0512

Gnomad4 OTH exome

AF:

0.0880

GnomAD4 genome

AF:

0.144

AC:

21969

AN:

152270

Hom.:

2963

Cov.:

AF XY:

0.143

AC XY:

10628

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.359

Gnomad4 AMR

AF:

0.0736

Gnomad4 ASJ

AF:

0.0729

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.0334

Gnomad4 NFE

AF:

0.0530

Gnomad4 OTH

AF:

0.132

Alfa

AF:

0.0701

Hom.:

1572

Bravo

AF:

0.156

TwinsUK

AF:

0.0580

AC:

215

ALSPAC

AF:

0.0537

AC:

207

ESP6500AA

AF:

0.344

AC:

1514

ESP6500EA

AF:

0.0523

AC:

450

ExAC

AF:

0.0979

AC:

11882

Asia WGS

AF:

0.174

AC:

604

AN:

3478

EpiCase

AF:

0.0495

EpiControl

AF:

0.0535

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group E

Uncertain:1Benign:3

Uncertain significance, no assertion criteria provided	curation	Leiden Open Variation Database	Feb 07, 2011	Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 06, 2016	- -
not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -
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

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.062

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.73

REVEL

Benign

0.050

Sift

Benign

0.89

Sift4G

Benign

0.53

Polyphen

0.0070

Vest4

0.043

MPC

0.14

ClinPred

0.0028

GERP RS

3.2

Varity_R

0.067

gMVP

0.046

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