chr6-35455764-G-T

Position:

chr6-35455764-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021922.3(FANCE):c.266G>T(p.Arg89Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000487 in 1,614,038 control chromosomes in the GnomAD database, including 5 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 5 hom. )

Consequence

FANCE
NM_021922.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.00100

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 (MetaRNN=0.007122487).

BP6

Variant 6-35455764-G-T is Benign according to our data. Variant chr6-35455764-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 134334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-35455764-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000532 (81/152270) while in subpopulation EAS AF= 0.0116 (60/5176). AF 95% confidence interval is 0.00924. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCE	NM_021922.3 linkuse as main transcript	c.266G>T	p.Arg89Leu	missense_variant	2/10	ENST00000229769.3	NP_068741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCE	ENST00000229769.3 linkuse as main transcript	c.266G>T	p.Arg89Leu	missense_variant	2/10	1	NM_021922.3	ENSP00000229769	P1

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000931

AC:

234

AN:

251374

Hom.:

AF XY:

0.000876

AC XY:

119

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0102

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000482

AC:

705

AN:

1461768

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

343

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0123

Gnomad4 SAS exome

AF:

0.000557

Gnomad4 FIN exome

AF:

0.000919

Gnomad4 NFE exome

AF:

0.0000620

Gnomad4 OTH exome

AF:

0.000828

GnomAD4 genome

AF:

0.000532

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0116

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0200

Hom.:

2307

Bravo

AF:

0.000461

ExAC

AF:

0.000923

AC:

112

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4Other:1

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	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1Other:1

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 03, 2017	- -
not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

FANCE: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.092

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0071

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.2

REVEL

Benign

0.039

Sift

Benign

1.0

Sift4G

Uncertain

0.010

Polyphen

0.067

Vest4

0.26

MVP

0.36

MPC

0.20

ClinPred

0.021

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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