X-14857956-TAATAAATA-TAATAAATAAATA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001018113.3(FANCB):c.1105-6_1105-3dupTATT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,065,970 control chromosomes in the GnomAD database, including 25 homozygotes. There are 597 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 19 hom., 246 hem., cov: 22)

Exomes 𝑓: 0.0018 ( 6 hom. 351 hem. )

Consequence

FANCB
NM_001018113.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.218

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-14857956-T-TAATA is Benign according to our data. Variant chrX-14857956-T-TAATA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 167060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00976 (1091/111735) while in subpopulation AFR AF = 0.0307 (942/30696). AF 95% confidence interval is 0.0291. There are 19 homozygotes in GnomAd4. There are 246 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCB	NM_001018113.3 link	c.1105-6_1105-3dupTATT		splice_region_variant, intron_variant	Intron 4 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.1105-3_1105-2insTATT		splice_region_variant, intron_variant	Intron 4 of 9		NM_001018113.3	ENSP00000498215.1

Frequencies

GnomAD3 genomes

AF:

0.00975

AC:

1089

AN:

111688

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0307

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00372

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00139

Gnomad SAS

AF:

0.000727

Gnomad FIN

AF:

0.000668

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.00801

GnomAD2 exomes

AF:

0.00250

AC:

444

AN:

177339

AF XY:

0.00117

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.00201

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000814

Gnomad FIN exome

AF:

0.000126

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.000689

GnomAD4 exome

AF:

0.00175

AC:

1670

AN:

954235

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

351

AN XY:

266053

show subpopulations

African (AFR)

AF:

0.0220

AC:

511

AN:

23277

American (AMR)

AF:

0.00230

AC:

AN:

34354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18277

East Asian (EAS)

AF:

0.000238

AC:

AN:

29460

South Asian (SAS)

AF:

0.000323

AC:

AN:

49558

European-Finnish (FIN)

AF:

0.000274

AC:

AN:

40163

Middle Eastern (MID)

AF:

0.00285

AC:

AN:

3154

European-Non Finnish (NFE)

AF:

0.00125

AC:

891

AN:

714726

Other (OTH)

AF:

0.00354

AC:

146

AN:

41266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

109

163

218

272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.00976

AC:

1091

AN:

111735

Hom.:

Cov.:

AF XY:

0.00723

AC XY:

246

AN XY:

34003

show subpopulations

African (AFR)

AF:

0.0307

AC:

942

AN:

30696

American (AMR)

AF:

0.00372

AC:

AN:

10491

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00140

AC:

AN:

3583

South Asian (SAS)

AF:

0.000729

AC:

AN:

2742

European-Finnish (FIN)

AF:

0.000668

AC:

AN:

5985

Middle Eastern (MID)

AF:

0.00461

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00162

AC:

AN:

53173

Other (OTH)

AF:

0.00792

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00113

Hom.:

Bravo

AF:

0.0119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 16, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 19, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Fanconi anemia

Benign:2

Sep 29, 2020

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia complementation group B

Benign:1

Feb 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Sep 30, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.22

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over