X-14850684-A-G

Variant names:

• chrX-14850684-A-G
• rs2905223
• NM_001018113.3:c.1327-10T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001018113.3(FANCB):​c.1327-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (11742 hom., 16080 hem., cov: 21)
  • Exomes 𝑓: 0.58 (120219 hom. 169168 hem.)
  • Failed GnomAD Quality Control
• Consequence: FANCB NM_001018113.3 intron
• Scores: Splicing: ADA: 0.00002456
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -1.27

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-14850684-A-G is Benign according to our data. Variant chrX-14850684-A-G is described in ClinVar as [Benign]. Clinvar id is 93467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-14850684-A-G is described in Lovd as [Benign]. Variant chrX-14850684-A-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCB	NM_001018113.3	c.1327-10T>C		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.1327-10T>C		intron_variant	Intron 6 of 9		NM_001018113.3	ENSP00000498215.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 58196 AN: 108757 Hom.: 11746 Cov.: 21 AF XY: 0.514 AC XY: 16063 AN XY: 31235

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.534

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.507

GnomAD3 exomes AF: 0.517 AC: 78766 AN: 152467 Hom.: 15122 AF XY: 0.516 AC XY: 23447 AN XY: 45399

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.438

Gnomad ASJ exome AF: 0.555

Gnomad EAS exome AF: 0.180

Gnomad SAS exome AF: 0.424

Gnomad FIN exome AF: 0.611

Gnomad NFE exome AF: 0.610

Gnomad OTH exome AF: 0.545

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.576 AC: 573309 AN: 995768 Hom.: 120219 Cov.: 18 AF XY: 0.574 AC XY: 169168 AN XY: 294908

Gnomad4 AFR exome AF: 0.478

Gnomad4 AMR exome AF: 0.447

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.149

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.610

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.535 AC: 58192 AN: 108802 Hom.: 11742 Cov.: 21 AF XY: 0.514 AC XY: 16080 AN XY: 31290

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.498

Alfa AF: 0.579 Hom.: 9715

Bravo AF: 0.527

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fanconi anemia complementation group B Benign:4

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:3

Oct 28, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fanconi anemia Benign:2

Dec 09, 2019

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

VACTERL association, X-linked, with or without hydrocephalus Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

X-linked central congenital hypothyroidism with late-onset testicular enlargement Benign:1

Feb 28, 2020

Leiden Open Variation Database

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: curation

Curator: Arleen D. Auerbach. Submitter to LOVD: Yu Sun. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs2905223; hg19: chrX-14868806; COSMIC: COSV60762278;