dbSNP rs6526990: FANCB:c.2487+17459G>A (chrX-14826201-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001410764.1(FANCB):c.2487+17459G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 111,444 control chromosomes in the GnomAD database, including 602 homozygotes. There are 2,103 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.069 ( 602 hom., 2103 hem., cov: 23)

Consequence

FANCB
NM_001410764.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.15

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
FANCB	NM_001410764.1 link	c.2487+17459G>A	intron_variant	Intron 10 of 12	NP_001397693.1
FANCB	XR_001755672.2 link	n.2762+17459G>A	intron_variant	Intron 10 of 14
FANCB	XR_001755673.2 link	n.6704+17459G>A	intron_variant	Intron 9 of 13

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
FANCB	ENST00000696353.1 link	c.2487+17459G>A	intron_variant	Intron 10 of 12	ENSP00000512574.1
FANCB	ENST00000696354.1 link	c.2487+17459G>A	intron_variant	Intron 10 of 10	ENSP00000512575.1
FANCB	ENST00000696322.1 link	n.*1232+17459G>A	intron_variant	Intron 9 of 9	ENSP00000512559.1

Frequencies

GnomAD3 genomes

AF:

0.0690

AC:

7687

AN:

111393

Hom.:

601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0308

Gnomad ASJ

AF:

0.00871

Gnomad EAS

AF:

0.00252

Gnomad SAS

AF:

0.00992

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0295

Gnomad NFE

AF:

0.00662

Gnomad OTH

AF:

0.0511

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0692

AC:

7711

AN:

111444

Hom.:

602

Cov.:

AF XY:

0.0625

AC XY:

2103

AN XY:

33674

show subpopulations

African (AFR)

AF:

0.223

AC:

6810

AN:

30496

American (AMR)

AF:

0.0308

AC:

323

AN:

10486

Ashkenazi Jewish (ASJ)

AF:

0.00871

AC:

AN:

2642

East Asian (EAS)

AF:

0.00253

AC:

AN:

3557

South Asian (SAS)

AF:

0.00995

AC:

AN:

2714

European-Finnish (FIN)

AF:

0.0127

AC:

AN:

5962

Middle Eastern (MID)

AF:

0.0278

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00662

AC:

352

AN:

53158

Other (OTH)

AF:

0.0557

AC:

AN:

1526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

224

448

673

897

1121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0248

Hom.:

452

Bravo

AF:

0.0790

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.13

(source)

DANN

Benign

0.43

PhyloP100

-2.1

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over