Variant 10-32912050-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

Variant links:

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]

ITGB1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB1	ENST00000302278.8 linkuse as main transcript	c.1544A>T	p.Tyr515Phe	missense_variant	12/16	1	NM_002211.4	P4	P05556-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727236

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.35

.;T;T

Eigen

Benign

-0.027

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.93

D;D;.

M_CAP

Benign

0.022

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.81

L;L;L

MutationTaster

Benign

0.63

D;D;D;D

PrimateAI

Benign

0.44

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over