Variant 1-63454964-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014288.5(ITGB3BP):c.259A>G(p.Met87Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000943 in 1,495,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

ITGB3BP
NM_014288.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.222

Variant links:

Genes affected

ITGB3BP (HGNC:6157): (integrin subunit beta 3 binding protein) This gene encodes a transcriptional coregulator that binds to and enhances the activity of members of the nuclear receptor families, thyroid hormone receptors and retinoid X receptors. This protein also acts as a corepressor of NF-kappaB-dependent signaling. This protein induces apoptosis in breast cancer cells through a caspase 2-mediated signaling pathway. This protein is also a component of the centromere-specific histone H3 variant nucleosome associated complex (CENP-NAC) and may be involved in mitotic progression by recruiting the histone H3 variant CENP-A to the centromere. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ITGB3BP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029866338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB3BP	NM_014288.5 linkuse as main transcript	c.259A>G	p.Met87Val	missense_variant	5/9	ENST00000271002.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB3BP	ENST00000271002.15 linkuse as main transcript	c.259A>G	p.Met87Val	missense_variant	5/9	1	NM_014288.5	P2	Q13352-1

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000114

AC:

AN:

245254

Hom.:

AF XY:

0.0000753

AC XY:

AN XY:

132774

show subpopulations

Gnomad AFR exome

AF:

0.000965

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000722

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000633

AC:

AN:

1343150

Hom.:

Cov.:

AF XY:

0.0000608

AC XY:

AN XY:

674722

show subpopulations

Gnomad4 AFR exome

AF:

0.000839

Gnomad4 AMR exome

AF:

0.0000912

Gnomad4 ASJ exome

AF:

0.0000395

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.0000887

GnomAD4 genome

AF:

0.000368

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000951

Hom.:

Bravo

AF:

0.000332

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000148

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.376A>G (p.M126V) alteration is located in exon 6 (coding exon 6) of the ITGB3BP gene. This alteration results from a A to G substitution at nucleotide position 376, causing the methionine (M) at amino acid position 126 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.34

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

-0.030

Eigen_PC

Benign

-0.063

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.5

N;D

REVEL

Benign

0.13

Sift

Benign

0.038

D;D

Sift4G

Uncertain

0.022

D;T

Polyphen

0.79

P;P

Vest4

0.35

MVP

0.64

MPC

0.21

ClinPred

0.033

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.23

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