rs761346761

Variant names:

Variant summary

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

The ENST00000650831.1(FANCB):c.199A>G(p.Ile67Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,168,081 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.000018 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000030 ( 0 hom. 7 hem. )

Consequence

FANCB
ENST00000650831.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.959

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=0.05709061).

BP6

Variant X-14865312-T-C is Benign according to our data. Variant chrX-14865312-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 456180.

BS2

High Hemizygotes in GnomAdExome4 at 7 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.199A>G	p.Ile67Val	missense	Exon 3 of 10	NP_001018123.1
FANCB	NM_001410764.1		c.199A>G	p.Ile67Val	missense	Exon 3 of 13	NP_001397693.1
FANCB	NM_001324162.2		c.199A>G	p.Ile67Val	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.199A>G	p.Ile67Val	missense	Exon 3 of 10	ENSP00000498215.1
FANCB	ENST00000324138.7	TSL:1	c.199A>G	p.Ile67Val	missense	Exon 2 of 9	ENSP00000326819.3
FANCB	ENST00000452869.2	TSL:1	c.199A>G	p.Ile67Val	missense	Exon 3 of 11	ENSP00000397849.2

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112425

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000942

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:

0.000657

GnomAD2 exomes

AF:

0.0000202

AC:

AN:

148467

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000527

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000283

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000303

AC:

AN:

1055656

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

340050

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24308

American (AMR)

AF:

0.0000380

AC:

AN:

26344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17135

East Asian (EAS)

AF:

0.00

AC:

AN:

29837

South Asian (SAS)

AF:

0.00

AC:

AN:

47375

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3927

European-Non Finnish (NFE)

AF:

0.0000364

AC:

AN:

823478

Other (OTH)

AF:

0.0000226

AC:

AN:

44168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.0000178

AC:

AN:

112425

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34583

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30953

American (AMR)

AF:

0.0000942

AC:

AN:

10620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3620

South Asian (SAS)

AF:

0.00

AC:

AN:

2768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6143

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53223

Other (OTH)

AF:

0.000657

AC:

AN:

1522

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000165

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 (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

0.075

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.19

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.097

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.54

M_CAP

Benign

0.0079

MetaRNN

Benign

0.057

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

PhyloP100

-0.96

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.46

REVEL

Benign

0.0090

Sift

Benign

0.32

Sift4G

Benign

0.34

Polyphen

0.0010

Vest4

0.11

MutPred

0.24

Gain of methylation at K68 (P = 0.0548)

MVP

0.12

MPC

0.083

ClinPred

0.081

GERP RS

-3.5

Varity_R

0.047

Mutation Taster

=97/3

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