10-32912050-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_002211.4(ITGB1):c.1544A>T(p.Tyr515Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITGB1 NM_002211.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22

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.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ITGB1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB1	NM_002211.4	c.1544A>T	p.Tyr515Phe	missense_variant	12/16	ENST00000302278.8
ITGB1	NM_033668.2	c.1544A>T	p.Tyr515Phe	missense_variant	11/16
ITGB1	NM_133376.3	c.1544A>T	p.Tyr515Phe	missense_variant	12/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB1	ENST00000302278.8	c.1544A>T	p.Tyr515Phe	missense_variant	12/16	1	NM_002211.4	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727236

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: 0.00

GnomAD4 genome Cov.: 33

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

Oct 25, 2023

The c.1544A>T (p.Y515F) alteration is located in exon 11 (coding exon 11) of the ITGB1 gene. This alteration results from a A to T substitution at nucleotide position 1544, causing the tyrosine (Y) at amino acid position 515 to be replaced by a phenylalanine (F). 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	0.086
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
Cadd	Uncertain	24
Dann	Benign	0.97
Eigen	Benign	-0.027
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D;D;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.81	L;L;L
MutationTaster	Benign	0.63	D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.38	N;N;N
REVEL	Benign	0.097
Sift	Benign	0.090	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.039	B;B;B
Vest4		0.31
MutPred		0.21		Gain of methylation at K518 (P = 0.0919);Gain of methylation at K518 (P = 0.0919);Gain of methylation at K518 (P = 0.0919);
MVP		0.61
MPC		0.71
ClinPred		0.40	T
GERP RS		6.1
Varity_R		0.073
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: -7

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: chr10-33200978;