Variant X-14865123-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBS2_Supporting

The NM_001018113.3(FANCB):c.388A>G(p.Met130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,204,716 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.0000082 ( 0 hom. 0 hem. )

Consequence

FANCB
NM_001018113.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.221

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.064989924).

BP6

Variant X-14865123-T-C is Benign according to our data. Variant chrX-14865123-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 246617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCB	NM_001018113.3 linkuse as main transcript	c.388A>G	p.Met130Val	missense_variant	3/10	ENST00000650831.1	NP_001018123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCB	ENST00000650831.1 linkuse as main transcript	c.388A>G	p.Met130Val	missense_variant	3/10		NM_001018113.3	ENSP00000498215	P2

Frequencies

GnomAD3 genomes

AF:

0.0000446

AC:

AN:

112226

Hom.:

Cov.:

AF XY:

0.0000582

AC XY:

AN XY:

34390

show subpopulations

Gnomad AFR

AF:

0.000162

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000112

AC:

AN:

177797

Hom.:

AF XY:

0.00

AC XY:

AN XY:

63089

show subpopulations

Gnomad AFR exome

AF:

0.000154

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000824

AC:

AN:

1092490

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

358616

show subpopulations

Gnomad4 AFR exome

AF:

0.000345

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000446

AC:

AN:

112226

Hom.:

Cov.:

AF XY:

0.0000582

AC XY:

AN XY:

34390

show subpopulations

Gnomad4 AFR

AF:

0.000162

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

This alteration is classified as likely 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. -

Fanconi anemia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.5

DANN

Benign

0.47

DEOGEN2

Benign

0.15

T;T;T

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.58

T;.;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.065

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.63

N;N;N

REVEL

Benign

0.036

Sift

Uncertain

0.023

D;D;D

Sift4G

Uncertain

0.020

D;D;D

Polyphen

0.0010

B;B;.

Vest4

0.20

MutPred

0.20

Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);

MVP

0.093

MPC

0.10

ClinPred

0.019

GERP RS

0.22

Varity_R

0.19

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