rs200161949

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001018113.3(FANCB):c.989T>C(p.Ile330Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000576 in 1,191,371 control chromosomes in the GnomAD database, including 1 homozygotes. There are 217 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., 11 hem., cov: 23)

Exomes 𝑓: 0.00059 ( 1 hom. 206 hem. )

Consequence

FANCB
NM_001018113.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:7

Conservation

PhyloP100: 5.66

Variant links:

Genes affected

FANCB (HGNC:3583): (FA complementation group B) This gene encodes a member of the Fanconi anemia complementation group B. This protein is assembled into a nucleoprotein complex that is involved in the repair of DNA lesions. Mutations in this gene can cause chromosome instability and VACTERL syndrome with hydrocephalus. [provided by RefSeq, Apr 2016]

FANCB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028166264).

BP6

Variant X-14859297-A-G is Benign according to our data. Variant chrX-14859297-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 197175.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=1, Uncertain_significance=1}. Variant chrX-14859297-A-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCB	NM_001018113.3 link	c.989T>C	p.Ile330Thr	missense_variant	Exon 4 of 10	ENST00000650831.1	NP_001018123.1	Q8NB91A0A024RBW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCB	ENST00000650831.1 link	c.989T>C	p.Ile330Thr	missense_variant	Exon 4 of 10		NM_001018113.3	ENSP00000498215.1		Q8NB91

Frequencies

GnomAD3 genomes

AF:

0.000474

AC:

AN:

111825

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

33987

show subpopulations

Gnomad AFR

AF:

0.0000649

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.000377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000640

Gnomad OTH

AF:

0.00200

GnomAD3 exomes

AF:

0.000504

AC:

AN:

182720

Hom.:

AF XY:

0.000490

AC XY:

AN XY:

67286

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.000268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000490

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000586

AC:

633

AN:

1079495

Hom.:

Cov.:

AF XY:

0.000594

AC XY:

206

AN XY:

346783

show subpopulations

Gnomad4 AFR exome

AF:

0.0000767

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.000208

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000652

Gnomad4 OTH exome

AF:

0.000704

GnomAD4 genome

AF:

0.000474

AC:

AN:

111876

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

34048

show subpopulations

Gnomad4 AFR

AF:

0.0000648

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.000377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000640

Gnomad4 OTH

AF:

0.00197

Alfa

AF:

0.000514

Hom.:

Bravo

AF:

0.000695

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000453

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:7

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 07, 2014

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FANCB: BP4, BS2 -

Fanconi anemia

Benign:2

Jun 20, 2021

Sema4, Sema4

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Apr 16, 2021

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FANCB-related disorder

Benign:1

Oct 31, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Uncertain

0.45

T;T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.66

T;.;T

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.028

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.3

M;M;.

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.26

Sift

Benign

0.10

T;T;T

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.11

B;B;.

Vest4

0.53

MVP

0.61

MPC

0.32

ClinPred

0.032

GERP RS

5.8

Varity_R

0.27

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