X-14843919-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001410764.1(FANCB):c.2228T>G(p.Phe743Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000408 in 1,200,821 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F743Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. 4 hem. )

Consequence

FANCB
NM_001410764.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 0.0300

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: 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020747423).

BP6

Variant X-14843919-A-C is Benign according to our data. Variant chrX-14843919-A-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 435139.

BS2

High Hemizygotes in GnomAd4 at 6 AR,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001410764.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FANCB	NM_001018113.3	MANE Select	c.2228T>G	p.Phe743Cys	missense	Exon 10 of 10	NP_001018123.1
FANCB	NM_001410764.1		c.2228T>G	p.Phe743Cys	missense	Exon 10 of 13	NP_001397693.1
FANCB	NM_001324162.2		c.2228T>G	p.Phe743Cys	missense	Exon 10 of 10	NP_001311091.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FANCB	ENST00000650831.1	MANE Select	c.2228T>G	p.Phe743Cys	missense	Exon 10 of 10	ENSP00000498215.1
FANCB	ENST00000324138.7	TSL:1	c.2228T>G	p.Phe743Cys	missense	Exon 9 of 9	ENSP00000326819.3
FANCB	ENST00000452869.2	TSL:1	c.2228T>G	p.Phe743Cys	missense	Exon 10 of 11	ENSP00000397849.2

Frequencies

GnomAD3 genomes

AF:

0.000286

AC:

AN:

111954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000949

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:

0.000661

GnomAD2 exomes

AF:

0.0000781

AC:

AN:

179232

AF XY:

0.0000621

show subpopulations

Gnomad AFR exome

AF:

0.000855

Gnomad AMR exome

AF:

0.0000373

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000248

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000156

AC:

AN:

1088813

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

354785

show subpopulations

African (AFR)

AF:

0.000574

AC:

AN:

26117

American (AMR)

AF:

0.00

AC:

AN:

34906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19232

East Asian (EAS)

AF:

0.00

AC:

AN:

30157

South Asian (SAS)

AF:

0.00

AC:

AN:

53519

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4095

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

834722

Other (OTH)

AF:

0.0000219

AC:

AN:

45745

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000286

AC:

AN:

112008

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

34174

show subpopulations

African (AFR)

AF:

0.000972

AC:

AN:

30854

American (AMR)

AF:

0.0000948

AC:

AN:

10552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2639

East Asian (EAS)

AF:

0.00

AC:

AN:

3570

South Asian (SAS)

AF:

0.00

AC:

AN:

2711

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6063

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53186

Other (OTH)

AF:

0.000653

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000298

ExAC

AF:

0.0000824

AC:

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fanconi anemia (2)

Inborn genetic diseases (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.8

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.17

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.67

M_CAP

Benign

0.0038

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

0.030

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.056

Sift

Benign

0.18

Sift4G

Benign

0.21

Polyphen

0.91

Vest4

0.15

MVP

0.15

MPC

0.15

ClinPred

0.14

GERP RS

1.9

Varity_R

0.12

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over