Variant X-14857956-TAATAAATA-TAATAAATAAATA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:5

Conservation

PhyloP100: 0.218

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 links:

FANCB (HGNC:):

FANCB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCB	NM_001018113.3 linkuse as main transcript	c.1105-6_1105-3dupTATT		splice_region_variant, intron_variant		ENST00000650831.1	NP_001018123.1	Q8NB91A0A024RBW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCB	ENST00000650831.1 linkuse as main transcript	c.1105-6_1105-3dupTATT		splice_region_variant, intron_variant			NM_001018113.3	ENSP00000498215.1		Q8NB91

Frequencies

GnomAD3 genomes

AF:

0.00975

AC:

1089

AN:

111688

Hom.:

Cov.:

AF XY:

0.00725

AC XY:

246

AN XY:

33946

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

GnomAD3 exomes

AF:

0.00250

AC:

444

AN:

177339

Hom.:

AF XY:

0.00117

AC XY:

AN XY:

63079

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 SAS exome

AF:

0.000284

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

Gnomad4 AFR exome

AF:

0.0220

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000238

Gnomad4 SAS exome

AF:

0.000323

Gnomad4 FIN exome

AF:

0.000274

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.00354

GnomAD4 genome

AF:

0.00976

AC:

1091

AN:

111735

Hom.:

Cov.:

AF XY:

0.00723

AC XY:

246

AN XY:

34003

show subpopulations

Gnomad4 AFR

AF:

0.0307

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00140

Gnomad4 SAS

AF:

0.000729

Gnomad4 FIN

AF:

0.000668

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.00792

Bravo

AF:

0.0119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Eurofins Ntd Llc (ga)	Mar 19, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 16, 2016	- -

Fanconi anemia

Benign:2

Benign, criteria provided, single submitter	curation	Sema4, Sema4	Sep 29, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2014

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over