NM_002211.4:c.1751A>T

Variant names:

• chr10-32911628-T-A
• NM_002211.4:c.1751A>T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_002211.4(ITGB1):​c.1751A>T​(p.Asn584Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITGB1 NM_002211.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.26

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 5 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
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.1751A>T	p.Asn584Ile	missense_variant	Exon 13 of 16	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.1751A>T	p.Asn584Ile	missense_variant	Exon 12 of 16		NP_391988.1
ITGB1	NM_133376.3	c.1751A>T	p.Asn584Ile	missense_variant	Exon 13 of 16		NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.1751A>T	p.Asn584Ile	missense_variant	Exon 13 of 16	1	NM_002211.4	ENSP00000303351.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.88	.;D;D
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.80	T;T;.
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.91	P;P;P
Vest4		0.68
MutPred		0.52		Loss of disorder (P = 0.0235);Loss of disorder (P = 0.0235);Loss of disorder (P = 0.0235);
MVP		0.87
MPC		1.5
ClinPred		0.97	D
GERP RS		5.9
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8
Varity_R		0.53
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-33200556;