Genetic Variant ITGB1:p.Arg676Pro (chr10-32910360-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002211.4(ITGB1):c.2027G>C(p.Arg676Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R676L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ITGB1
NM_002211.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.04

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4 link	c.2027G>C	p.Arg676Pro	missense_variant	Exon 14 of 16	ENST00000302278.8	NP_002202.2	P05556-1
ITGB1	NM_033668.2 link	c.2027G>C	p.Arg676Pro	missense_variant	Exon 13 of 16		NP_391988.1	P05556-5
ITGB1	NM_133376.3 link	c.2027G>C	p.Arg676Pro	missense_variant	Exon 14 of 16		NP_596867.1	P05556-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8 link	c.2027G>C	p.Arg676Pro	missense_variant	Exon 14 of 16	1	NM_002211.4	ENSP00000303351.3		P05556-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447614

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720694

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33182

American (AMR)

AF:

0.00

AC:

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26048

East Asian (EAS)

AF:

0.00

AC:

AN:

39572

South Asian (SAS)

AF:

0.00

AC:

AN:

85870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1099242

Other (OTH)

AF:

0.00

AC:

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

.;T;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;.

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.90

D;D;D

MetaSVM

Uncertain

0.77

MutationAssessor

Uncertain

2.4

M;M;M

PhyloP100

5.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.1

N;N;N

REVEL

Pathogenic

0.76

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.77

MutPred

0.70

Gain of methylation at K672 (P = 0.0478);Gain of methylation at K672 (P = 0.0478);Gain of methylation at K672 (P = 0.0478);

MVP

0.91

MPC

2.1

ClinPred

0.94

GERP RS

4.7

Varity_R

0.42

gMVP

0.90

Mutation Taster

=45/55

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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10-32910360-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over