chrX-14850684-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 93467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018113.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCB	NM_001018113.3	MANE Select	c.1327-10T>C		intron	N/A	NP_001018123.1
	FANCB	NM_001410764.1		c.1327-10T>C		intron	N/A	NP_001397693.1
	FANCB	NM_001324162.2		c.1327-10T>C		intron	N/A	NP_001311091.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCB	ENST00000650831.1	MANE Select	c.1327-10T>C		intron	N/A	ENSP00000498215.1
	FANCB	ENST00000324138.7	TSL:1	c.1327-10T>C		intron	N/A	ENSP00000326819.3
	FANCB	ENST00000452869.2	TSL:1	c.1327-10T>C		intron	N/A	ENSP00000397849.2

Frequencies

GnomAD3 genomes AF: 0.535 AC: 58196 AN: 108757 Hom.: 11746 Cov.: 21

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

GnomAD2 exomes AF: 0.517 AC: 78766 AN: 152467 AF XY: 0.516

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 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

African (AFR) AF: 0.478 AC: 11466 AN: 24006

American (AMR) AF: 0.447 AC: 14680 AN: 32814

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 10228 AN: 18258

East Asian (EAS) AF: 0.149 AC: 4357 AN: 29209

South Asian (SAS) AF: 0.427 AC: 21290 AN: 49825

European-Finnish (FIN) AF: 0.611 AC: 23802 AN: 38953

Middle Eastern (MID) AF: 0.558 AC: 2061 AN: 3692

European-Non Finnish (NFE) AF: 0.610 AC: 461737 AN: 756560

Other (OTH) AF: 0.558 AC: 23688 AN: 42451

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

African (AFR) AF: 0.477 AC: 14263 AN: 29915

American (AMR) AF: 0.479 AC: 4892 AN: 10220

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1416 AN: 2603

East Asian (EAS) AF: 0.171 AC: 600 AN: 3512

South Asian (SAS) AF: 0.387 AC: 992 AN: 2563

European-Finnish (FIN) AF: 0.584 AC: 3162 AN: 5414

Middle Eastern (MID) AF: 0.538 AC: 113 AN: 210

European-Non Finnish (NFE) AF: 0.602 AC: 31443 AN: 52228

Other (OTH) AF: 0.498 AC: 734 AN: 1473

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

Aug 10, 2021

Genome-Nilou Lab

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

not specified Benign:3

Oct 28, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

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

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

Dec 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.50
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2905223; hg19: chrX-14868806; COSMIC: COSV60762278;