X-14850514-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001018113.3(FANCB):c.1487C>G(p.Ser496Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000276 in 1,087,126 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S496F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Consequence

FANCB
NM_001018113.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.62

Publications

0 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: ClinGen, G2P, 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
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

FANCB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3279592).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018113.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FANCB	NM_001018113.3	MANE Select	c.1487C>G	p.Ser496Cys	missense	Exon 7 of 10	NP_001018123.1	Q8NB91
FANCB	NM_001410764.1		c.1487C>G	p.Ser496Cys	missense	Exon 7 of 13	NP_001397693.1	A0A8Q3WL66
FANCB	NM_001324162.2		c.1487C>G	p.Ser496Cys	missense	Exon 7 of 10	NP_001311091.1	Q8NB91

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FANCB	ENST00000650831.1	MANE Select	c.1487C>G	p.Ser496Cys	missense	Exon 7 of 10	ENSP00000498215.1	Q8NB91
FANCB	ENST00000324138.7	TSL:1	c.1487C>G	p.Ser496Cys	missense	Exon 6 of 9	ENSP00000326819.3	Q8NB91
FANCB	ENST00000452869.2	TSL:1	c.1487C>G	p.Ser496Cys	missense	Exon 7 of 11	ENSP00000397849.2	C9J5X9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1087126

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

353580

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26200

American (AMR)

AF:

0.00

AC:

AN:

35188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19310

East Asian (EAS)

AF:

0.00

AC:

AN:

30108

South Asian (SAS)

AF:

0.00

AC:

AN:

53889

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40505

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4039

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

832193

Other (OTH)

AF:

0.0000657

AC:

AN:

45694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fanconi anemia (1)

Fanconi anemia complementation group B;C2931228:VACTERL association, X-linked, with or without hydrocephalus (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.72

M_CAP

Benign

0.011

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.6

PhyloP100

4.6

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.16

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.31

MutPred

0.38

Loss of disorder (P = 0.0048)

MVP

0.45

MPC

0.50

ClinPred

0.94

GERP RS

4.7

Varity_R

0.41

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over