Variant 10-32907089-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002211.4(ITGB1):c.2331+1279G>A variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000603 in 1,359,486 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

ITGB1
NM_002211.4 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

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 -4 ACMG points.

BS2

High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ITGB1	NM_002211.4 linkuse as main transcript	c.2331+1279G>A		intron_variant		ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2 linkuse as main transcript	c.2386G>A	p.Gly796Arg	missense_variant	15/16		NP_391988.1
ITGB1	NM_133376.3 linkuse as main transcript	c.2331+1279G>A		intron_variant			NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8 linkuse as main transcript	c.2331+1279G>A		intron_variant		1	NM_002211.4	ENSP00000303351	P4	P05556-1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000294

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000648

AC:

AN:

247076

Hom.:

AF XY:

0.0000751

AC XY:

AN XY:

133216

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.0000347

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000801

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1207542

Hom.:

Cov.:

AF XY:

0.0000535

AC XY:

AN XY:

598438

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000274

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000516

Gnomad4 OTH exome

AF:

0.0000914

GnomAD4 genome

AF:

0.000132

AC:

AN:

151944

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.000151

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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 04, 2023

The c.2386G>A (p.G796R) alteration is located in exon 15 (coding exon 15) of the ITGB1 gene. This alteration results from a G to A substitution at nucleotide position 2386, causing the glycine (G) at amino acid position 796 to be replaced by an arginine (R). 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

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.33

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.31

MutationTaster

Benign

0.86

D;D;D;D

PROVEAN

Benign

1.0

REVEL

Uncertain

0.50

Sift

Benign

0.13

Sift4G

Benign

0.36

Polyphen

1.0

Vest4

0.71

MutPred

0.53

Gain of MoRF binding (P = 0.0191);

MVP

0.71

ClinPred

0.16

GERP RS

6.0

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