Genetic Variant FANCB:p.Glu444Gly (chrX-14850670-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001018113.3(FANCB):c.1331A>G(p.Glu444Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E444V) has been classified as Benign.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

FANCB
NM_001018113.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Fanconi anemia complementation group B
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
VACTERL association, X-linked, with or without hydrocephalus
Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
VACTERL with hydrocephalus
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FANCB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06877598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCB	NM_001018113.3 link	c.1331A>G	p.Glu444Gly	missense_variant	Exon 7 of 10	ENST00000650831.1	NP_001018123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCB	ENST00000650831.1 link	c.1331A>G	p.Glu444Gly	missense_variant	Exon 7 of 10		NM_001018113.3	ENSP00000498215.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000607

AC:

AN:

164637

AF XY:

0.0000190

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000138

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1027803

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

304819

African (AFR)

AF:

0.00

AC:

AN:

24976

American (AMR)

AF:

0.00

AC:

AN:

33901

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18685

East Asian (EAS)

AF:

0.00

AC:

AN:

29753

South Asian (SAS)

AF:

0.00

AC:

AN:

51158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3857

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

782018

Other (OTH)

AF:

0.00

AC:

AN:

43617

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.8

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.24

T;T;T

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.39

T;.;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.069

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;.

PhyloP100

1.3

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.034

Sift

Uncertain

0.013

D;D;D

Sift4G

Benign

0.30

T;T;T

Polyphen

0.0040

B;B;.

Vest4

0.23

MutPred

0.27

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

MVP

0.12

MPC

0.13

ClinPred

0.066

GERP RS

-1.9

Varity_R

0.058

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over