X-14857956-TAATAAATA-TAATAAATAAATA

Variant names:

• chrX-14857956-T-TAATA
• rs398123537
• NM_001018113.3:c.1105-6_1105-3dupTATT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.218

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-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 rank	MANE	Protein	UniProt
FANCB	NM_001018113.3	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	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.: 19 Cov.: 22 AF XY: 0.00725 AC XY: 246 AN XY: 33946

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.: 2 AF XY: 0.00117 AC XY: 74 AN XY: 63079

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.: 6 Cov.: 17 AF XY: 0.00132 AC XY: 351 AN XY: 266053

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.: 19 Cov.: 22 AF XY: 0.00723 AC XY: 246 AN XY: 34003

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:6

Revision: criteria provided, multiple submitters, no conflicts

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

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 29, 2020

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

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. -

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

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs398123537; hg19: chrX-14876078;