dbSNP rs184385334: FANCB:c.2165+10A>T (chrX-14844493-T-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBS2_Supporting

The NM_001018113.3(FANCB):c.2165+10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,123,235 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00011 ( 0 hom. 30 hem. )

Consequence

FANCB
NM_001018113.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.523

Publications

3 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-14844493-T-A is Benign according to our data. Variant chrX-14844493-T-A is described in ClinVar as Benign. ClinVar VariationId is 456182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCB	NM_001018113.3 link	c.2165+10A>T		intron_variant	Intron 9 of 9	ENST00000650831.1	NP_001018123.1	Q8NB91A0A024RBW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCB	ENST00000650831.1 link	c.2165+10A>T		intron_variant	Intron 9 of 9		NM_001018113.3	ENSP00000498215.1		Q8NB91

Frequencies

GnomAD3 genomes

AF:

0.0000626

AC:

AN:

111766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00196

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:

0.000341

AC:

AN:

181976

AF XY:

0.000238

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00441

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

112

AN:

1011416

Hom.:

Cov.:

AF XY:

0.0000995

AC XY:

AN XY:

301616

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24734

American (AMR)

AF:

0.00

AC:

AN:

35118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18820

East Asian (EAS)

AF:

0.00318

AC:

AN:

29832

South Asian (SAS)

AF:

0.000134

AC:

AN:

52279

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3929

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

762943

Other (OTH)

AF:

0.000231

AC:

AN:

43263

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.0000626

AC:

AN:

111819

Hom.:

Cov.:

AF XY:

0.0000589

AC XY:

AN XY:

33981

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30788

American (AMR)

AF:

0.00

AC:

AN:

10600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00197

AC:

AN:

3556

South Asian (SAS)

AF:

0.00

AC:

AN:

2689

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53102

Other (OTH)

AF:

0.00

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

Bravo

AF:

0.000166

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group B

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia

Benign:1

Jan 19, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

(source)

DANN

Benign

0.56

PhyloP100

0.52

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over