Variant chr10-32912060-T-C 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_002211.4(ITGB1):c.1534A>G(p.Met512Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,880 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: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ITGB1
NM_002211.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

Variant links:

Genes affected

ITGB1 (HGNC:6153): (integrin subunit beta 1) Integrins are heterodimeric proteins made up of alpha and beta subunits. At least 18 alpha and 8 beta subunits have been described in mammals. Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. This gene encodes a beta subunit. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ITGB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25946274).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ITGB1	NM_002211.4 linkuse as main transcript	c.1534A>G	p.Met512Val	missense_variant	12/16	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2 linkuse as main transcript	c.1534A>G	p.Met512Val	missense_variant	11/16		NP_391988.1
ITGB1	NM_133376.3 linkuse as main transcript	c.1534A>G	p.Met512Val	missense_variant	12/16		NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8 linkuse as main transcript	c.1534A>G	p.Met512Val	missense_variant	12/16	1	NM_002211.4	ENSP00000303351	P4	P05556-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251096

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 01, 2024

The c.1534A>G (p.M512V) alteration is located in exon 11 (coding exon 11) of the ITGB1 gene. This alteration results from a A to G substitution at nucleotide position 1534, causing the methionine (M) at amino acid position 512 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

0.30

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

.;T;T

Eigen

Benign

-0.070

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;D;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.3

L;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.044

D;D;D

Sift4G

Uncertain

0.054

T;T;T

Polyphen

0.099

B;B;B

Vest4

0.46

MutPred

0.20

Loss of phosphorylation at S509 (P = 0.237);Loss of phosphorylation at S509 (P = 0.237);Loss of phosphorylation at S509 (P = 0.237);

MVP

0.80

MPC

0.82

ClinPred

0.31

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.32

gMVP

0.87

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