10-32920297-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1 PM2 PP2 BP4_Moderate

The NM_002211.4(ITGB1):c.1217A>C(p.Asn406Thr) 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. 14/21 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: 4.44

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 3 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity ITB1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ITGB1
• BP4: Computational evidence support a benign effect (MetaRNN=0.12702826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB1	NM_002211.4	c.1217A>C	p.Asn406Thr	missense_variant	10/16	ENST00000302278.8
ITGB1	NM_033668.2	c.1217A>C	p.Asn406Thr	missense_variant	9/16
ITGB1	NM_133376.3	c.1217A>C	p.Asn406Thr	missense_variant	10/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB1	ENST00000302278.8	c.1217A>C	p.Asn406Thr	missense_variant	10/16	1	NM_002211.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 08, 2023

The c.1217A>C (p.N406T) alteration is located in exon 9 (coding exon 9) of the ITGB1 gene. This alteration results from a A to C substitution at nucleotide position 1217, causing the asparagine (N) at amino acid position 406 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	0.079
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	21
Dann	Benign	0.95
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.097
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D;D;.
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.26	N;N;N
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.54	N;N;N
REVEL	Benign	0.092
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.016	B;B;B
Vest4		0.27
MutPred		0.46		Loss of ubiquitination at K402 (P = 0.1055);Loss of ubiquitination at K402 (P = 0.1055);Loss of ubiquitination at K402 (P = 0.1055);
MVP		0.52
MPC		0.80
ClinPred		0.85	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-33209225;