X-14845063-A-T

Variant names:

Variant summary

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

The ENST00000650831.1(FANCB):c.1720T>A(p.Cys574Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 1,206,086 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. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.000021 ( 0 hom. 7 hem. )

Consequence

FANCB
ENST00000650831.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 0.807

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=0.023682296).

BP6

Variant X-14845063-A-T is Benign according to our data. Variant chrX-14845063-A-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 408160.

BS2

High Hemizygotes in GnomAd4 at 3 AR,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650831.1. 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.1720T>A	p.Cys574Ser	missense	Exon 8 of 10	NP_001018123.1
FANCB	NM_001410764.1		c.1720T>A	p.Cys574Ser	missense	Exon 8 of 13	NP_001397693.1
FANCB	NM_001324162.2		c.1720T>A	p.Cys574Ser	missense	Exon 8 of 10	NP_001311091.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FANCB	ENST00000650831.1	MANE Select	c.1720T>A	p.Cys574Ser	missense	Exon 8 of 10	ENSP00000498215.1
FANCB	ENST00000324138.7	TSL:1	c.1720T>A	p.Cys574Ser	missense	Exon 7 of 9	ENSP00000326819.3
FANCB	ENST00000452869.2	TSL:1	c.1720T>A	p.Cys574Ser	missense	Exon 8 of 11	ENSP00000397849.2

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

111980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000617

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD2 exomes

AF:

0.0000655

AC:

AN:

183094

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.000608

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000210

AC:

AN:

1094106

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

359650

show subpopulations

African (AFR)

AF:

0.000494

AC:

AN:

26324

American (AMR)

AF:

0.000142

AC:

AN:

35193

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19361

East Asian (EAS)

AF:

0.00

AC:

AN:

30179

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4124

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

838391

Other (OTH)

AF:

0.0000870

AC:

AN:

45960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000170

AC:

AN:

111980

Hom.:

Cov.:

AF XY:

0.0000878

AC XY:

AN XY:

34170

show subpopulations

African (AFR)

AF:

0.000617

AC:

AN:

30814

American (AMR)

AF:

0.00

AC:

AN:

10582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2637

East Asian (EAS)

AF:

0.00

AC:

AN:

3579

South Asian (SAS)

AF:

0.00

AC:

AN:

2730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53150

Other (OTH)

AF:

0.00

AC:

AN:

1501

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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:

0.0000712

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

FANCB-related disorder (1)

Fanconi anemia (1)

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

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.1

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.15

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.50

M_CAP

Benign

0.0027

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.81

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.2

REVEL

Benign

0.045

Sift

Benign

0.55

Sift4G

Benign

0.62

Polyphen

0.018

Vest4

0.080

MutPred

0.39

Gain of disorder (P = 0.0052)

MVP

0.18

MPC

0.12

ClinPred

0.013

GERP RS

2.8

Varity_R

0.13

Mutation Taster

=99/1

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over