chr10-32910334-G-T

Variant names:

• chr10-32910334-G-T
• NM_002211.4:c.2053C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002211.4(ITGB1):​c.2053C>A​(p.Pro685Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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: 0.313
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08838868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.2053C>A	p.Pro685Thr	missense_variant	Exon 14 of 16	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.2053C>A	p.Pro685Thr	missense_variant	Exon 13 of 16		NP_391988.1
ITGB1	NM_133376.3	c.2053C>A	p.Pro685Thr	missense_variant	Exon 14 of 16		NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.2053C>A	p.Pro685Thr	missense_variant	Exon 14 of 16	1	NM_002211.4	ENSP00000303351.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2053C>A (p.P685T) alteration is located in exon 13 (coding exon 13) of the ITGB1 gene. This alteration results from a C to A substitution at nucleotide position 2053, causing the proline (P) at amino acid position 685 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.096
DEOGEN2	Benign	0.20	.;T;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.82	T;T;.
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.088	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.69	N;N;N
PhyloP100		0.31
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.27	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.23
MutPred		0.47		Loss of catalytic residue at P685 (P = 0.025);Loss of catalytic residue at P685 (P = 0.025);Loss of catalytic residue at P685 (P = 0.025);
MVP		0.53
MPC		0.87
ClinPred		0.057	T
GERP RS		2.4
Varity_R		0.028
gMVP		0.42
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr10-33199262;