10-32911497-G-C

Position:

• chr10-32911497-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002211.4(ITGB1):​c.1882C>G​(p.Gln628Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ITGB1 NM_002211.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20243609).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.1882C>G	p.Gln628Glu	missense_variant	13/16	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.1882C>G	p.Gln628Glu	missense_variant	12/16		NP_391988.1
ITGB1	NM_133376.3	c.1882C>G	p.Gln628Glu	missense_variant	13/16		NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.1882C>G	p.Gln628Glu	missense_variant	13/16	1	NM_002211.4	ENSP00000303351	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.1882C>G (p.Q628E) alteration is located in exon 12 (coding exon 12) of the ITGB1 gene. This alteration results from a C to G substitution at nucleotide position 1882, causing the glutamine (Q) at amino acid position 628 to be replaced by a glutamic acid (E). 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	0.083
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	.;T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.032
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;D;.
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.33	N;N;N
MutationTaster	Benign	0.98	N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.40	N;N;N
REVEL	Benign	0.069
Sift	Uncertain	0.014	D;D;D
Sift4G	Uncertain	0.046	D;D;D
Polyphen		0.0040	B;B;B
Vest4		0.25
MutPred		0.34		Gain of ubiquitination at K624 (P = 0.1235);Gain of ubiquitination at K624 (P = 0.1235);Gain of ubiquitination at K624 (P = 0.1235);
MVP		0.55
MPC		0.86
ClinPred		0.76	D
GERP RS		4.7
Varity_R		0.15
gMVP		0.62

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

Other links and lift over

dbSNP: rs934163727; hg19: chr10-33200425;