Genetic Variant NM_002211.4:c.2027G>A (chr10-32910360-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002211.4(ITGB1):c.2027G>A(p.Arg676Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000563 in 1,599,718 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ITGB1
NM_002211.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.04

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4 link	c.2027G>A	p.Arg676Gln	missense_variant	Exon 14 of 16	ENST00000302278.8	NP_002202.2	P05556-1
ITGB1	NM_033668.2 link	c.2027G>A	p.Arg676Gln	missense_variant	Exon 13 of 16		NP_391988.1	P05556-5
ITGB1	NM_133376.3 link	c.2027G>A	p.Arg676Gln	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>A	p.Arg676Gln	missense_variant	Exon 14 of 16	1	NM_002211.4	ENSP00000303351.3		P05556-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250528

AF XY:

0.00000738

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000553

AC:

AN:

1447614

Hom.:

Cov.:

AF XY:

0.00000694

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:

0.0000233

AC:

AN:

85870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.000523

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000273

AC:

AN:

1099242

Other (OTH)

AF:

0.00

AC:

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.0000655

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

.;T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D;.

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.73

D;D;D

MetaSVM

Uncertain

0.62

MutationAssessor

Uncertain

2.7

M;M;M

PhyloP100

5.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.48

N;N;N

REVEL

Uncertain

0.53

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.97

D;D;D

Vest4

0.47

MutPred

0.66

Gain of methylation at K672 (P = 0.0559);Gain of methylation at K672 (P = 0.0559);Gain of methylation at K672 (P = 0.0559);

MVP

0.86

MPC

1.0

ClinPred

0.81

GERP RS

4.7

Varity_R

0.058

gMVP

0.68

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_002211.4:c.2027G>A

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