Variant 10-32910360-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_002211.4(ITGB1):c.2027G>T(p.Arg676Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,599,716 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

ITGB1
NM_002211.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04

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 -3 ACMG points.

PP2

Missense variant where missense usually causes diseases, ITGB1

BS2

High AC in GnomAd at 54 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ITGB1	NM_002211.4 linkuse as main transcript	c.2027G>T	p.Arg676Leu	missense_variant	14/16	ENST00000302278.8
ITGB1	NM_033668.2 linkuse as main transcript	c.2027G>T	p.Arg676Leu	missense_variant	13/16
ITGB1	NM_133376.3 linkuse as main transcript	c.2027G>T	p.Arg676Leu	missense_variant	14/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB1	ENST00000302278.8 linkuse as main transcript	c.2027G>T	p.Arg676Leu	missense_variant	14/16	1	NM_002211.4	P4	P05556-1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

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:

0.0000588

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000184

AC:

AN:

250528

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135436

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.000899

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000926

Gnomad NFE exome

AF:

0.0000882

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000108

AC:

157

AN:

1447612

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

720692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000829

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.0000919

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000355

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00308

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000461

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000234

AC:

ExAC

AF:

0.000107

AC:

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 07, 2022

The c.2027G>T (p.R676L) alteration is located in exon 13 (coding exon 13) of the ITGB1 gene. This alteration results from a G to T substitution at nucleotide position 2027, causing the arginine (R) at amino acid position 676 to be replaced by a leucine (L). 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

Uncertain

0.56

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Uncertain

0.11

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;.

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Uncertain

0.64

MutationAssessor

Benign

0.79

N;N;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.10

N;N;N

REVEL

Pathogenic

0.65

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.94

P;D;D

Vest4

0.81

MVP

0.93

MPC

1.1

ClinPred

0.096

GERP RS

4.7

Varity_R

0.12

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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