dbSNP rs993307430: FANCB:p.Ser496Phe (chrX-14850514-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4BS2_Supporting

The NM_001018113.3(FANCB):c.1487C>T(p.Ser496Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000184 in 1,087,125 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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. S496C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )

Consequence

FANCB
NM_001018113.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.388739).

BS2

High Hemizygotes in GnomAdExome4 at 2 AR,XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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>T	p.Ser496Phe	missense	Exon 7 of 10	NP_001018123.1	Q8NB91
FANCB	NM_001410764.1		c.1487C>T	p.Ser496Phe	missense	Exon 7 of 13	NP_001397693.1	A0A8Q3WL66
FANCB	NM_001324162.2		c.1487C>T	p.Ser496Phe	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>T	p.Ser496Phe	missense	Exon 7 of 10	ENSP00000498215.1	Q8NB91
FANCB	ENST00000324138.7	TSL:1	c.1487C>T	p.Ser496Phe	missense	Exon 6 of 9	ENSP00000326819.3	Q8NB91
FANCB	ENST00000452869.2	TSL:1	c.1487C>T	p.Ser496Phe	missense	Exon 7 of 11	ENSP00000397849.2	C9J5X9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000184

AC:

AN:

1087125

Hom.:

Cov.:

AF XY:

0.00000566

AC XY:

AN XY:

353579

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:

0.0000186

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:

0.00000120

AC:

AN:

832192

Other (OTH)

AF:

0.00

AC:

AN:

45694

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fanconi anemia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

M_CAP

Benign

0.021

MetaRNN

Benign

0.39

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.6

PhyloP100

4.6

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.27

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.054

Polyphen

1.0

Vest4

0.29

MutPred

0.37

Loss of disorder (P = 0.0077)

MVP

0.36

MPC

0.53

ClinPred

0.99

GERP RS

4.7

Varity_R

0.65

Mutation Taster

=80/20

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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