Variant rs587777210 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_012278.4(ITGB1BP2):c.938C>G(p.Ala313Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 1,209,399 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 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 Uncertain significance (no stars).

Frequency

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

Exomes 𝑓: 0.000053 ( 0 hom. 21 hem. )

Consequence

ITGB1BP2
NM_012278.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

ITGB1BP2 (HGNC:6154): (integrin subunit beta 1 binding protein 2) This gene encodes a protein with two cysteine and histidine-rich (CHORD) domains, PXXP motifs, YXXI/P motifs, putative SH2 and SH3 domain binding motifs, and an acidic region at the C-terminus that can bind calcium. Two hybrid analysis showed that this protein interacts with the cytoplasmic domain of the beta 1 integrin subunit and is thought to act as a chaperone protein. Studies in the mouse ortholog of this gene indicate that absence of this gene in mouse results in failed cardiac hypertrophy in response to mechanical stress. Alternative splicing results in multiple transcript variants encoding different isoforms, including an isoform that lacks several domains, including one of the CHORD domains. [provided by RefSeq, May 2017]

ITGB1BP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10649791).

BS2

High Hemizygotes in GnomAdExome4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB1BP2	NM_012278.4 linkuse as main transcript	c.938C>G	p.Ala313Gly	missense_variant	11/11	ENST00000373829.8	NP_036410.1	Q9UKP3-1
ITGB1BP2	NM_001303277.3 linkuse as main transcript	c.569C>G	p.Ala190Gly	missense_variant	8/8		NP_001290206.1
ITGB1BP2	XM_047441988.1 linkuse as main transcript	c.635C>G	p.Ala212Gly	missense_variant	9/9		XP_047297944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB1BP2	ENST00000373829.8 linkuse as main transcript	c.938C>G	p.Ala313Gly	missense_variant	11/11	1	NM_012278.4	ENSP00000362935.3		Q9UKP3-1
ITGB1BP2	ENST00000538820.1 linkuse as main transcript	c.884C>G	p.Ala295Gly	missense_variant	10/10	1		ENSP00000440289.1		Q9UKP3-2

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111699

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33873

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:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000439

AC:

AN:

182363

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

66941

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000985

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000528

AC:

AN:

1097700

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

363068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000653

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111699

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33873

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:

0.0000564

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jan 10, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.12

T;.

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.024

Sift

Benign

0.13

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.016

B;.

Vest4

0.089

MVP

0.92

MPC

0.36

ClinPred

0.032

GERP RS

2.5

Varity_R

0.15

gMVP

0.16

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