rs142101123

Variant summary

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

The NM_001018113.3(FANCB):c.262G>A(p.Gly88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,147,117 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., 23 hem., cov: 23)

Exomes 𝑓: 0.000058 ( 0 hom. 13 hem. )

Consequence

FANCB
NM_001018113.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.36

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=0.011479914).

BP6

Variant X-14865249-C-T is Benign according to our data. Variant chrX-14865249-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 526482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-14865249-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000556 (62/111524) while in subpopulation AFR AF= 0.00172 (53/30737). AF 95% confidence interval is 0.00135. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCB	NM_001018113.3 linkuse as main transcript	c.262G>A	p.Gly88Arg	missense_variant	3/10	ENST00000650831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCB	ENST00000650831.1 linkuse as main transcript	c.262G>A	p.Gly88Arg	missense_variant	3/10		NM_001018113.3	P2

Frequencies

GnomAD3 genomes

AF:

0.000556

AC:

AN:

111478

Hom.:

Cov.:

AF XY:

0.000681

AC XY:

AN XY:

33754

show subpopulations

Gnomad AFR

AF:

0.00173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000475

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:

0.00

Gnomad OTH

AF:

0.00266

GnomAD3 exomes

AF:

0.000159

AC:

AN:

138557

Hom.:

AF XY:

0.000128

AC XY:

AN XY:

46701

show subpopulations

Gnomad AFR exome

AF:

0.00151

Gnomad AMR exome

AF:

0.000230

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000579

AC:

AN:

1035593

Hom.:

Cov.:

AF XY:

0.0000396

AC XY:

AN XY:

328299

show subpopulations

Gnomad4 AFR exome

AF:

0.00180

Gnomad4 AMR exome

AF:

0.000205

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000246

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

AF:

0.000556

AC:

AN:

111524

Hom.:

Cov.:

AF XY:

0.000680

AC XY:

AN XY:

33810

show subpopulations

Gnomad4 AFR

AF:

0.00172

Gnomad4 AMR

AF:

0.000475

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00263

Alfa

AF:

0.000408

Hom.:

Bravo

AF:

0.000586

ESP6500AA

AF:

0.000784

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000141

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia

Benign:2

Likely benign, criteria provided, single submitter	curation	Sema4, Sema4	Feb 05, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

Cadd

Benign

Dann

Benign

0.82

DEOGEN2

Uncertain

0.49

T;T;T

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.73

T;.;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

L;L;.

MutationTaster

Benign

0.78

D;D

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.072

Sift

Benign

0.42

T;T;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.096

B;B;.

Vest4

0.32

MutPred

0.49

Gain of catalytic residue at G88 (P = 0.0365);Gain of catalytic residue at G88 (P = 0.0365);Gain of catalytic residue at G88 (P = 0.0365);

MVP

0.16

MPC

0.23

ClinPred

0.048

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.29

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