chrX-14850676-TA-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001018113.3(FANCB):c.1327-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,048,224 control chromosomes in the GnomAD database, including 294 homozygotes. There are 3,223 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 143 hom., 929 hem., cov: 21)

Exomes 𝑓: 0.0098 ( 151 hom. 2294 hem. )

Consequence

FANCB
NM_001018113.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.476

Publications

2 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.

BP6

Variant X-14850676-TA-T is Benign according to our data. Variant chrX-14850676-TA-T is described in ClinVar as Benign. ClinVar VariationId is 93468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCB	NM_001018113.3 link	c.1327-3delT		splice_region_variant, intron_variant	Intron 6 of 9	ENST00000650831.1	NP_001018123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCB	ENST00000650831.1 link	c.1327-3delT		splice_region_variant, intron_variant	Intron 6 of 9		NM_001018113.3	ENSP00000498215.1

Frequencies

GnomAD3 genomes

AF:

0.0356

AC:

3757

AN:

105487

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.00156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00972

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.0176

Gnomad NFE

AF:

0.00624

Gnomad OTH

AF:

0.0229

GnomAD2 exomes

AF:

0.0184

AC:

2302

AN:

125253

AF XY:

0.0132

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00716

Gnomad FIN exome

AF:

0.0194

Gnomad NFE exome

AF:

0.00740

Gnomad OTH exome

AF:

0.0143

GnomAD4 exome

AF:

0.00976

AC:

9204

AN:

942709

Hom.:

151

Cov.:

AF XY:

0.00860

AC XY:

2294

AN XY:

266641

show subpopulations

African (AFR)

AF:

0.114

AC:

2595

AN:

22853

American (AMR)

AF:

0.0105

AC:

313

AN:

29747

Ashkenazi Jewish (ASJ)

AF:

0.00140

AC:

AN:

17082

East Asian (EAS)

AF:

0.00152

AC:

AN:

25600

South Asian (SAS)

AF:

0.00921

AC:

412

AN:

44744

European-Finnish (FIN)

AF:

0.0160

AC:

601

AN:

37467

Middle Eastern (MID)

AF:

0.0166

AC:

AN:

3547

European-Non Finnish (NFE)

AF:

0.00637

AC:

4596

AN:

721609

Other (OTH)

AF:

0.0141

AC:

565

AN:

40060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

294

588

881

1175

1469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

214

428

642

856

1070

<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:

0.0357

AC:

3768

AN:

105515

Hom.:

143

Cov.:

AF XY:

0.0313

AC XY:

929

AN XY:

29659

show subpopulations

African (AFR)

AF:

0.109

AC:

3147

AN:

28862

American (AMR)

AF:

0.0170

AC:

165

AN:

9712

Ashkenazi Jewish (ASJ)

AF:

0.00156

AC:

AN:

2570

East Asian (EAS)

AF:

0.00

AC:

AN:

3355

South Asian (SAS)

AF:

0.00980

AC:

AN:

2450

European-Finnish (FIN)

AF:

0.0130

AC:

AN:

5001

Middle Eastern (MID)

AF:

0.0146

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.00626

AC:

321

AN:

51278

Other (OTH)

AF:

0.0276

AC:

AN:

1412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

122

244

366

488

610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.00721

Hom.:

Bravo

AF:

0.0388

Asia WGS

AF:

0.0180

AC:

AN:

2514

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 09, 2019

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

VACTERL with hydrocephalus

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Apr 02, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

Nov 24, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Fanconi anemia complementation group B

Benign:1

Sep 24, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FANCB-related disorder

Benign:1

Jul 01, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

not provided

Benign:1

Mar 08, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Fanconi Anemia, X-Linked

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hereditary cancer-predisposing syndrome

Benign:1

Jul 09, 2025

Molecular Diagnostics Laboratory, Catalan Institute of Oncology

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BA1, BP4 c.1327-3del, located in intron 6 close to a canonical splice site of the FANCB gene. The variant allele was found in 1643/14059 alleles (68 homozygous), with a filter allele frequency of 11.3% at 95% confidence, within the African population in the gnomAD v2.1.1 database (non-cancer dataset)(BA1). The SpliceAI algorithm predicts no significant impact on splicing (BP4). To our knowledge, functional studies have not been reported for this variant. In addition, this variant has been reported in ClinVar (9x benign) and in LOVD database (2x benign). Based on the currently available information, c.1327-3del is classified as a benign variant according to ACMG guidelines.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.48

Mutation Taster

=99/1

polymorphism (auto)

(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