chrX-14850630-G-A

Position:

chrX-14850630-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001018113.3(FANCB):c.1371C>T(p.Val457Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000364 in 1,188,001 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 127 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., 6 hem., cov: 22)

Exomes 𝑓: 0.00037 ( 0 hom. 121 hem. )

Consequence

FANCB
NM_001018113.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.118

Variant links:

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 links:

FANCB (HGNC:):

FANCB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-14850630-G-A is Benign according to our data. Variant chrX-14850630-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 198442.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=3}.

BP7

Synonymous conserved (PhyloP=-0.118 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0003 (33/109925) while in subpopulation NFE AF= 0.000493 (26/52740). AF 95% confidence interval is 0.000345. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCB	NM_001018113.3 linkuse as main transcript	c.1371C>T	p.Val457Val	synonymous_variant	7/10	ENST00000650831.1	NP_001018123.1	Q8NB91A0A024RBW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCB	ENST00000650831.1 linkuse as main transcript	c.1371C>T	p.Val457Val	synonymous_variant	7/10		NM_001018113.3	ENSP00000498215.1		Q8NB91

Frequencies

GnomAD3 genomes

AF:

0.000300

AC:

AN:

109875

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

AN XY:

32243

show subpopulations

Gnomad AFR

AF:

0.000133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000195

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000493

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000394

AC:

AN:

180421

Hom.:

AF XY:

0.000322

AC XY:

AN XY:

65121

show subpopulations

Gnomad AFR exome

AF:

0.0000771

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000189

Gnomad NFE exome

AF:

0.000832

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000370

AC:

399

AN:

1078076

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

121

AN XY:

345950

show subpopulations

Gnomad4 AFR exome

AF:

0.0000384

Gnomad4 AMR exome

AF:

0.0000286

Gnomad4 ASJ exome

AF:

0.0000521

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000223

Gnomad4 NFE exome

AF:

0.000444

Gnomad4 OTH exome

AF:

0.000462

GnomAD4 genome

AF:

0.000300

AC:

AN:

109925

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

AN XY:

32303

show subpopulations

Gnomad4 AFR

AF:

0.000133

Gnomad4 AMR

AF:

0.000195

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000179

Gnomad4 NFE

AF:

0.000493

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000314

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 03, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2021	- -

Fanconi anemia

Benign:2

Likely benign, criteria provided, single submitter	curation	Sema4, Sema4	Mar 14, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Fanconi anemia complementation group B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

VACTERL association, X-linked, with or without hydrocephalus

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.84

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over