rs142101123

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001018113.3(FANCB):c.262G>A(p.Gly88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,147,117 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., 23 hem., cov: 23)

Exomes 𝑓: 0.000058 ( 0 hom. 13 hem. )

Consequence

FANCB
NM_001018113.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.36

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011479914).

BP6

Variant X-14865249-C-T is Benign according to our data. Variant chrX-14865249-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 526482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 23 AR,XL gene

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
FANCB	NM_001018113.3	MANE Select	c.262G>A	p.Gly88Arg	missense	Exon 3 of 10	NP_001018123.1
FANCB	NM_001410764.1		c.262G>A	p.Gly88Arg	missense	Exon 3 of 13	NP_001397693.1
FANCB	NM_001324162.2		c.262G>A	p.Gly88Arg	missense	Exon 3 of 10	NP_001311091.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FANCB	ENST00000650831.1	MANE Select	c.262G>A	p.Gly88Arg	missense	Exon 3 of 10	ENSP00000498215.1
FANCB	ENST00000324138.7	TSL:1	c.262G>A	p.Gly88Arg	missense	Exon 2 of 9	ENSP00000326819.3
FANCB	ENST00000452869.2	TSL:1	c.262G>A	p.Gly88Arg	missense	Exon 3 of 11	ENSP00000397849.2

Frequencies

GnomAD3 genomes

AF:

0.000556

AC:

AN:

111478

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000475

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:

0.00266

GnomAD2 exomes

AF:

0.000159

AC:

AN:

138557

AF XY:

0.000128

show subpopulations

Gnomad AFR exome

AF:

0.00151

Gnomad AMR exome

AF:

0.000230

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:

0.0000579

AC:

AN:

1035593

Hom.:

Cov.:

AF XY:

0.0000396

AC XY:

AN XY:

328299

show subpopulations

African (AFR)

AF:

0.00180

AC:

AN:

23862

American (AMR)

AF:

0.000205

AC:

AN:

24375

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15951

East Asian (EAS)

AF:

0.00

AC:

AN:

29690

South Asian (SAS)

AF:

0.00

AC:

AN:

44637

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38453

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

3847

European-Non Finnish (NFE)

AF:

0.00000246

AC:

AN:

811414

Other (OTH)

AF:

0.000184

AC:

AN:

43364

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

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:

0.000556

AC:

AN:

111524

Hom.:

Cov.:

AF XY:

0.000680

AC XY:

AN XY:

33810

show subpopulations

African (AFR)

AF:

0.00172

AC:

AN:

30737

American (AMR)

AF:

0.000475

AC:

AN:

10537

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2632

East Asian (EAS)

AF:

0.00

AC:

AN:

3598

South Asian (SAS)

AF:

0.00

AC:

AN:

2668

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52935

Other (OTH)

AF:

0.00263

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.00123

Hom.:

Bravo

AF:

0.000586

ESP6500AA

AF:

0.000784

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000141

AC:

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fanconi anemia (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Uncertain

0.49

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.73

M_CAP

Benign

0.0091

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

PhyloP100

2.4

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.072

Sift

Benign

0.42

Sift4G

Benign

0.35

Polyphen

0.096

Vest4

0.32

MutPred

0.49

Gain of catalytic residue at G88 (P = 0.0365)

MVP

0.16

MPC

0.23

ClinPred

0.048

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.29

Mutation Taster

=96/4

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