Variant rs138192474 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001018113.3(FANCB):c.1079C>T(p.Thr360Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000447 in 1,185,339 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T360A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000047 ( 0 hom. 11 hem. )

Consequence

FANCB
NM_001018113.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.90

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12936479).

BP6

Variant X-14859207-G-A is Benign according to our data. Variant chrX-14859207-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 456175.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Hemizygotes in GnomAdExome4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCB	NM_001018113.3 linkuse as main transcript	c.1079C>T	p.Thr360Met	missense_variant	4/10	ENST00000650831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCB	ENST00000650831.1 linkuse as main transcript	c.1079C>T	p.Thr360Met	missense_variant	4/10		NM_001018113.3	P2

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111483

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33705

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:

0.000842

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:

0.0000720

AC:

AN:

180442

Hom.:

AF XY:

0.00

AC XY:

AN XY:

65230

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000187

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000292

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000466

AC:

AN:

1073804

Hom.:

Cov.:

AF XY:

0.0000321

AC XY:

AN XY:

342870

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000267

Gnomad4 SAS exome

AF:

0.0000378

Gnomad4 FIN exome

AF:

0.0000742

Gnomad4 NFE exome

AF:

0.0000365

Gnomad4 OTH exome

AF:

0.0000442

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111535

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33767

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000845

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Fanconi anemia

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	curation	Sema4, Sema4	Feb 05, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

D;D;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

T;.;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.9

L;L;.

MutationTaster

Benign

0.97

D;D

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Benign

0.19

Sift

Benign

0.040

D;D;D

Sift4G

Benign

0.071

T;T;T

Polyphen

0.99

D;D;.

Vest4

0.33

MVP

0.35

MPC

0.41

ClinPred

0.25

GERP RS

5.0

Varity_R

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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