rs398123537

chrX-14857956-TAATAAATA-TchrX-14857956-TAATAAATA-TAATAchrX-14857956-TAATAAATA-TAATAAATAAATAchrX-14857956-TAATAAATA-TAATAAATAAATAAATA

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.1105-10_1105-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,066,049 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., 6 hem., cov: 22)
  • Exomes 𝑓: 0.000051 (0 hom. 11 hem.)
• Consequence: FANCB NM_001018113.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.429

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-TAATAAATA-T is Benign according to our data. Variant chrX-14857956-TAATAAATA-T is described in ClinVar as [Likely_benign]. Clinvar id is 281376.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 = 0.000242 (27/111748) while in subpopulation AFR AF= 0.000782 (24/30708). AF 95% confidence interval is 0.000539. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCB	NM_001018113.3	c.1105-10_1105-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000650831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCB	ENST00000650831.1	c.1105-10_1105-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001018113.3	P2

Frequencies

GnomAD3 genomes AF: 0.000242 AC: 27 AN: 111701 Hom.: 0 Cov.: 22 AF XY: 0.000177 AC XY: 6 AN XY: 33955

Gnomad AFR AF: 0.000783

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000286

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000152 AC: 27 AN: 177339 Hom.: 0 AF XY: 0.000111 AC XY: 7 AN XY: 63079

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.0000380

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000877

Gnomad OTH exome AF: 0.000230

GnomAD4 exome AF: 0.0000513 AC: 49 AN: 954301 Hom.: 0 AF XY: 0.0000413 AC XY: 11 AN XY: 266117

Gnomad4 AFR exome AF: 0.00120

Gnomad4 AMR exome AF: 0.000146

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000202

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.000145

GnomAD4 genome AF: 0.000242 AC: 27 AN: 111748 Hom.: 0 Cov.: 22 AF XY: 0.000176 AC XY: 6 AN XY: 34012

Gnomad4 AFR AF: 0.000782

Gnomad4 AMR AF: 0.000286

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000110 Hom.: 5

Bravo AF: 0.000544

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fanconi anemia Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 15, 2024	- -
Likely benign, criteria provided, single submitter	curation	Sema4, Sema4	Oct 13, 2021	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 24, 2015

- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2016

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

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 24, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Fanconi anemia complementation group B;C2931228:VACTERL association, X-linked, with or without hydrocephalus Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 10, 2022

- -

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;