rs41309679

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001018113.3(FANCB):​c.1004G>A​(p.Gly335Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0731 in 1,187,007 control chromosomes in the GnomAD database, including 2,526 homozygotes. There are 27,854 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 155 hom., 1766 hem., cov: 23)
Exomes 𝑓: 0.075 ( 2371 hom. 26088 hem. )

Consequence

FANCB
NM_001018113.3 missense

Scores

4
6
6

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 4.56
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0026280582).
BP6
Variant X-14859282-C-T is Benign according to our data. Variant chrX-14859282-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0796 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FANCBNM_001018113.3 linkc.1004G>A p.Gly335Glu missense_variant Exon 4 of 10 ENST00000650831.1 NP_001018123.1 Q8NB91A0A024RBW1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FANCBENST00000650831.1 linkc.1004G>A p.Gly335Glu missense_variant Exon 4 of 10 NM_001018113.3 ENSP00000498215.1 Q8NB91

Frequencies

GnomAD3 genomes
AF:
0.0546
AC:
6078
AN:
111377
Hom.:
156
Cov.:
23
AF XY:
0.0526
AC XY:
1769
AN XY:
33625
show subpopulations
Gnomad AFR
AF:
0.0101
Gnomad AMI
AF:
0.00872
Gnomad AMR
AF:
0.0406
Gnomad ASJ
AF:
0.105
Gnomad EAS
AF:
0.000561
Gnomad SAS
AF:
0.0624
Gnomad FIN
AF:
0.0763
Gnomad MID
AF:
0.0684
Gnomad NFE
AF:
0.0816
Gnomad OTH
AF:
0.0674
GnomAD3 exomes
AF:
0.0617
AC:
11246
AN:
182122
Hom.:
311
AF XY:
0.0656
AC XY:
4379
AN XY:
66726
show subpopulations
Gnomad AFR exome
AF:
0.0103
Gnomad AMR exome
AF:
0.0256
Gnomad ASJ exome
AF:
0.0896
Gnomad EAS exome
AF:
0.000435
Gnomad SAS exome
AF:
0.0720
Gnomad FIN exome
AF:
0.0775
Gnomad NFE exome
AF:
0.0843
Gnomad OTH exome
AF:
0.0667
GnomAD4 exome
AF:
0.0750
AC:
80647
AN:
1075579
Hom.:
2371
Cov.:
25
AF XY:
0.0758
AC XY:
26088
AN XY:
344073
show subpopulations
Gnomad4 AFR exome
AF:
0.00980
Gnomad4 AMR exome
AF:
0.0287
Gnomad4 ASJ exome
AF:
0.0928
Gnomad4 EAS exome
AF:
0.000434
Gnomad4 SAS exome
AF:
0.0782
Gnomad4 FIN exome
AF:
0.0808
Gnomad4 NFE exome
AF:
0.0812
Gnomad4 OTH exome
AF:
0.0681
GnomAD4 genome
AF:
0.0545
AC:
6072
AN:
111428
Hom.:
155
Cov.:
23
AF XY:
0.0524
AC XY:
1766
AN XY:
33686
show subpopulations
Gnomad4 AFR
AF:
0.0101
Gnomad4 AMR
AF:
0.0405
Gnomad4 ASJ
AF:
0.105
Gnomad4 EAS
AF:
0.000563
Gnomad4 SAS
AF:
0.0615
Gnomad4 FIN
AF:
0.0763
Gnomad4 NFE
AF:
0.0816
Gnomad4 OTH
AF:
0.0665
Alfa
AF:
0.0797
Hom.:
3987
Bravo
AF:
0.0510
TwinsUK
AF:
0.0863
AC:
320
ALSPAC
AF:
0.0723
AC:
209
ESP6500AA
AF:
0.0149
AC:
57
ESP6500EA
AF:
0.0842
AC:
566
ExAC
AF:
0.0663
AC:
8054

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Fanconi anemia complementation group B Benign:4
Dec 19, 2024
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jul 07, 2023
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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. -

Oct 17, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:2
-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Dec 10, 2021
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Fanconi anemia Benign:2
Feb 26, 2020
Sema4, Sema4
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: curation

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:2
Jan 15, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30679340) -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Inborn genetic diseases Benign:1
Nov 24, 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. -

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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.65
D;D;T
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.79
T;.;T
MetaRNN
Benign
0.0026
T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Pathogenic
2.9
M;M;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-6.9
D;D;D
REVEL
Uncertain
0.32
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.22
MPC
0.58
ClinPred
0.019
T
GERP RS
5.8
Varity_R
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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.

Other links and lift over

dbSNP: rs41309679; hg19: chrX-14877404; COSMIC: COSV60758740; API