rs143131218

Positions:

chrX-14843695-T-C

Variant summary

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

The NM_001018113.3(FANCB):c.2452A>G(p.Arg818Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000527 in 1,209,146 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 193 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.00054 ( 0 hom. 184 hem. )

Consequence

FANCB
NM_001018113.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.60

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06629488).

BP6

Variant X-14843695-T-C is Benign according to our data. Variant chrX-14843695-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 246615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-14843695-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000358 (40/111821) while in subpopulation NFE AF= 0.000715 (38/53164). AF 95% confidence interval is 0.000535. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCB	NM_001018113.3 linkuse as main transcript	c.2452A>G	p.Arg818Gly	missense_variant	10/10	ENST00000650831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCB	ENST00000650831.1 linkuse as main transcript	c.2452A>G	p.Arg818Gly	missense_variant	10/10		NM_001018113.3	P2

Frequencies

GnomAD3 genomes

AF:

0.000358

AC:

AN:

111821

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

AN XY:

33985

show subpopulations

Gnomad AFR

AF:

0.0000650

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000715

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000290

AC:

AN:

183032

Hom.:

AF XY:

0.000340

AC XY:

AN XY:

67588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.000601

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.000544

AC:

597

AN:

1097325

Hom.:

Cov.:

AF XY:

0.000507

AC XY:

184

AN XY:

362725

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

0.000679

Gnomad4 OTH exome

AF:

0.000391

GnomAD4 genome

AF:

0.000358

AC:

AN:

111821

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

AN XY:

33985

show subpopulations

Gnomad4 AFR

AF:

0.0000650

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000715

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000569

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000321

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 11, 2024	- -
Likely benign, criteria provided, single submitter	curation	Sema4, Sema4	Nov 08, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 06, 2017

- -

Fanconi anemia complementation group B

Benign:1

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. -

FANCB-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 28, 2021

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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

FANCB: BP4, BS2 -

VACTERL association, X-linked, with or without hydrocephalus

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T;T

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.71

T;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Benign

0.20

Sift

Benign

0.085

T;T;D

Sift4G

Uncertain

0.021

D;D;D

Polyphen

0.76

P;P;.

Vest4

0.26

MVP

0.19

MPC

0.31

ClinPred

0.087

GERP RS

1.6

Varity_R

0.19

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