X-14796872-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_001410764.1(FANCB):​c.2654G>A​(p.Trp885*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 110,081 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 21)

Consequence

FANCB
NM_001410764.1 stop_gained

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.659
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 Uncertain_significance. Variant got 4 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0487 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FANCBNM_001410764.1 linkc.2654G>A p.Trp885* stop_gained Exon 12 of 13 NP_001397693.1
FANCBXR_001755672.2 linkn.2929G>A non_coding_transcript_exon_variant Exon 12 of 15
FANCBXR_001755673.2 linkn.6871G>A non_coding_transcript_exon_variant Exon 11 of 14

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FANCBENST00000696353.1 linkc.2654G>A p.Trp885* stop_gained Exon 12 of 13 ENSP00000512574.1 A0A8Q3WL66
FANCBENST00000696354 linkc.*271G>A 3_prime_UTR_variant Exon 11 of 11 ENSP00000512575.1 A0A8Q3SJA8
FANCBENST00000696322.1 linkn.*1659G>A non_coding_transcript_exon_variant Exon 10 of 10 ENSP00000512559.1 A0A8Q3SIN2

Frequencies

GnomAD3 genomes
AF:
0.0000273
AC:
3
AN:
110081
Hom.:
0
Cov.:
21
AF XY:
0.0000309
AC XY:
1
AN XY:
32311
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000567
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0000273
AC:
3
AN:
110081
Hom.:
0
Cov.:
21
AF XY:
0.0000309
AC XY:
1
AN XY:
32311
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000567
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023FANCB: PVS1:Moderate -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Pathogenic
27
DANN
Benign
0.68

Splicing

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: rs1417748431; hg19: chrX-14814994; API