X-14850676-TAAA-TAA

Variant names:

• chrX-14850676-TA-T
• rs202067682
• NM_001018113.3:c.1327-3delT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.476

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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	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	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.: 21 AF XY: 0.0311 AC XY: 921 AN XY: 29617

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

GnomAD3 exomes AF: 0.0184 AC: 2302 AN: 125253 Hom.: 59 AF XY: 0.0132 AC XY: 470 AN XY: 35629

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 SAS exome AF: 0.0124

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.: 19 AF XY: 0.00860 AC XY: 2294 AN XY: 266641

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.00140

Gnomad4 EAS exome AF: 0.00152

Gnomad4 SAS exome AF: 0.00921

Gnomad4 FIN exome AF: 0.0160

Gnomad4 NFE exome AF: 0.00637

Gnomad4 OTH exome AF: 0.0141

GnomAD4 genome AF: 0.0357 AC: 3768 AN: 105515 Hom.: 143 Cov.: 21 AF XY: 0.0313 AC XY: 929 AN XY: 29659

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0170

Gnomad4 ASJ AF: 0.00156

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00980

Gnomad4 FIN AF: 0.0130

Gnomad4 NFE AF: 0.00626

Gnomad4 OTH AF: 0.0276

Bravo AF: 0.0388

Asia WGS AF: 0.0180 AC: 44 AN: 2514

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not specified Benign:1

Apr 02, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

VACTERL with hydrocephalus Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

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. -

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

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs202067682; hg19: chrX-14868798;